tbuckley/cabot-search huggingface dataset:
Abstract PR07: Neutralizing the activity of murine TGF-β receptor 2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis
Authors: Katherine T. Ostapoff, Bercin Kutluk Cenik, Miao Wang, Risheng Ye, Xiaohing Xu, Desiree Nugent, Michelle Hagopian, Mary Topalovski, Lee B. Rivera, Kyla D. Carroll, Rolf A. Brekken
Journal: Cancer Research (2015)

Abstract Elevated levels of TGF-β are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result the TGF-β pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGF-β remains challenging because TGF-β has tumor suppressor functions in many epithelial malignancies including pancreatic cancer. In fact, direct neutralization of TGF-β promotes tumor progression of genetic murine models of pancreatic cancer. Here we report that neutralizing the activity of murine TGF-β receptor 2 using a monoclonal antibody (2G8) has potent anti-metastatic activity in orthotopic human tumor xenografts, syngenic tumors and a genetic model of pancreatic cancer. 2G8 induced an anti-metastatic stromal phenotype by increasing pro-inflammatory macrophages and NK cells and concomitantly decreasing anti-inflammatory macrophages, MDSCs and activated fibroblasts. These stromal specific changes resulted in tumor cell epithelial differentiation and a potent reduction in metastases. We conclude that TGF-β signaling within stromal cells participates directly in tumor cell phenotype and pancreatic cancer progression. Thus, strategies that inhibit TGF-β dependent effector functions of stromal cells could be efficacious for the therapy of pancreatic tumors. This abstract is also presented as Poster A38. Citation Format: Katherine T. Ostapoff, Bercin Kutluk Cenik, Miao Wang, Risheng Ye, Xiaohing Xu, Desiree Nugent, Michelle Hagopian, Mary Topalovski, Lee B. Rivera, Kyla D. Carroll, Rolf A. Brekken. Neutralizing the activity of murine TGF-β receptor 2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR07. doi:10.1158/1538-7445.CHTME14-PR07
Prevention of Typhoid Fever.
Authors: T. F. Campbell
Journal: JAMA (1904)

Cody, Neb., Jan. 12, 1904. <h3>To the Editor:</h3> —In reading the excellent paper and discussion in the last issue ofThe Journal, on prevention of typhoid, I wish to add the boiling as well as scalding of all dishes and tableware. In this remote, ranching, watershed locality typhoid is commencing to occur (imported). Hotel knives and forks, etc., seem conveyors from transients to residents. Cases guarded as above with, of course, other precautions, have been limited to one in a family, while those not under such care have spread.
THE DIAGNOSIS OF EARLY CANCEROUS CHANGES IN PEPTIC ULCER
Authors: ARTHUR L. BLOOMFIELD
Journal: JAMA (1935)

The discovery that an apparently benign gastric ulcer is in reality malignant is made often enough to justify the most strenuous efforts to avert such a tragedy. That this feeling is widespread at present is indicated by the abundant literature on the subject. Most of the papers, however, assert or imply that carelessness on the part of the physician is largely responsible and that something useful could be done if he did not stand idly by and allow the patient to drift into the late and hopeless stages of cancer; the thesis is sustained that careful study of people with ulcers which appear to be benign should make it possible to detect early malignant change and to effect a cure by prompt radical operation. It is my purpose in this paper to analyze this position and to see whether in fact it is a sound one.  I will consider first
Initiation of Obstetrics in Massachusetts.
Authors: Ephraim Cutter
Journal: JAMA (1899)

New York, March 22, 1899. <h3>To the Editor:</h3> —Apropos of an item under this heading, in a recentJournal, my father, Benjamin Cutter, M.D., Woburn, Mass. (obit. March 9, 1864), told me that in the last century women died so frequently in childbirth in Massachusetts that the men arose in wrath and compelled the physicians to practice midwifery and replace the midwives who were so unskiful; also that "John Brooks, M.A., Yale, 1781, and Harv., 1787, M.D., Harv., 1810, LL.D., Harv., 1817, president of the Massachusetts Medical Society, governor of Massachusetts," a noted military surgeon and friend of Washington, first responded to the imperative call and used his influence in its behalf. Soon unnecessary deaths ceased to devastate the homes of the "Old Bay State" of their glories (I Cor. ii, 7) and of their Queens of Motherhood.
CHLOROPHYLL AND DEODORIZATION
Authors: John W. Hein
Journal: JAMA (1953)

<h3>To the Editor:—</h3> An editorial entitled "Chlorophyll and Deodorization" in the Oct. 24 issue ofThe Journalquoted incorrectly from my paper presented before the American Dental Association annual meeting on Sept. 29, 1953. The correct quotation, with the word "protective" reinserted, was "Claims that toothpastes containing chlorophyll can give a protective deodorizing effect for several hours should be viewed with suspicion." The point I was trying to make, and which is missed in the misquotation, is that, since most of the toothpaste placed in the mouth on a toothbrush is quickly diluted by water and saliva, it is expecting a little too much that the amount remaining in the mouth after several hours will offer important protection against new odor agents placed in the mouth. While the deodorizing properties of chlorophyll derivatives have not been a major concern of my research with these materials since 1948, it has been
[169] OSTEOPONTIN EXPRESSION IN HEPATOCELLULAR CARCINOMA IS AN INDEPENDENT PREDICTOR OF SURVIVAL AFTER OLT FOR LOCALLY ADVANCED HCC
Authors: M. Peck-Radosavljevic, X. Wang, K. Schmid, W. Sieghart, M. Bodingbauer, F. Wrba, S. Rasoul-Rockenschaub
Journal: Journal of Hepatology (2007)
Use of enteral vancomycin for meticillin resistant Staphylococcus aureus (MRSA) in intensive care
Authors: L. Silvestri, M. A. de la Cal, E. Cerda, M. Viviani, H. K. F. van Saene
Journal: BMJ (2014)

Coia and colleagues cite two interventions aimed at reducing carriage of meticillin resistant Staphylococcus aureus (MRSA)—intranasal mupirocin and chlorhexidine bathing.1 They did not, however, mention that enteral vancomycin can control MRSA overgrowth, …
P-selectin/ICAM-1 double mutant mice: acute emigration of neutrophils into the peritoneum is completely absent but is normal into pulmonary alveoli.
Authors: D C Bullard, L Qin, I Lorenzo, W M Quinlin, N A Doyle, R Bosse, D Vestweber, C M Doerschuk, A L Beaudet
Journal: Journal of Clinical Investigation (1995)

Neutrophil emigration during an inflammatory response is mediated through interactions between adhesion molecules on endothelial cells and neutrophils.P-Selectin mediates rolling or slowing of neutrophils, while intercellular adhe- sion molecule-i (ICAM-1) contributes to the firm adhesion and emigration of neutrophils.Removing the function of either molecule partially prevents neutrophil emigration.To analyze further the role of P-selectin and ICAM-1, we have generated a line of mice with mutations in both of these molecules.While mice with either mutation alone show a 60-70% reduction in acute neutrophil emigration into the peritoneum during Streptococcus pneumoniae-induced peritonitis, double mutant mice show a complete loss of neutrophil emigration.In contrast, neutrophil emigration into the alveolar spaces during acute S. pneumoniae-induced pneumonia is normal in double mutant mice.These data demonstrate organ-specific differences, since emigra- tion into the peritoneum requires both adhesion molecules while emigration into the lung requires neither.In the peritoneum, P-selectin-independent and ICAM-1-independent adhesive mechanisms permit reduced emigration when one of these molecules is deficient, but P-selectin-independent mechanisms cannot lead to ICAM-1-independent firm ad- hesion and emigration.(
Genetic variation associated with plasma von Willebrand factor levels and the risk of incident venous thrombosis
Authors: Nicholas L. Smith, Kenneth M. Rice, Edwin G. Bovill, Mary Cushman, Joshua C. Bis, Barbara McKnight, Thomas Lumley, Nicole L. Glazer, Astrid van Hylckama Vlieg, Weihong Tang, Abbas Dehghan, David P. Strachan, Christopher J. O'Donnell, Jerome I. Rotter, Susan R. Heckbert, Bruce M. Psaty, Frits R. Rosendaal
Journal: Blood (2010)
Present and Future Treatment of Myasthenia Gravis
Authors: Daniel B. Drachman
Journal: New England Journal of Medicine (1987)

More than half a century ago, Mary Walker — a registrar in an obscure outlying London hospital—carried out a nonrandomized, nonblinded, uncontrolled, but highly successful trial of physostigmine in a patient with myasthenia gravis. Hailed in the press as the "Miracle of St. Alfege's Hospital," her discovery of the beneficial effect of this anticholinesterase agent provided evidence for a defect of neuromuscular transmission in myasthenia gravis and led to the use of similar drugs in the treatment of the disease.Since that time, and particularly during the past 15 years, knowledge of the pathophysiology of myasthenia gravis and its treatment . . .
THE FIRST YEAR OF THE SECTION ON GASTRO-ENTEROLOGY AND PROCTOLOGY
Authors: ANTHONY BASSLER
Journal: JAMA (1918)

The activities manifested at the first meeting of this section last year proved the wisdom of the House of Delegates in its establishment. Constantly spreading interest in it since that time is reason enough for its necessity and assures a progressive success. Although many of our gastro-enterologists and proctologists are now serving the country in efficient war work, the program, because of the rapidly increasing numbers of men interested in these fields, in quality and extent is but a small part of what was easily possible. Throughout the breadth of our beloved country, general practitioners, internists, surgeons and others are keenly in search of knowledge on these subjects, and they feel that this is a forum of first importance in which to help them. The House of Delegates builded well and it seems a pleasure on the part of many Fellows of the Association to prove it. In doing this
Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1
Authors: Gerd Fätkenheuer, Anton L Pozniak, Margaret A Johnson, Andreas Plettenberg, Schlomo Staszewski, Andy I M Hoepelman, Michael S Saag, Frank D Goebel, Jürgen K Rockstroh, Bruce J Dezube, Tim M Jenkins, Christine Medhurst, John F Sullivan, Caroline Ridgway, Samantha Abel, Ian T James, Mike Youle, Elna van der Ryst
Journal: Nature Medicine (2005)
Modulation of insulinlike growth factor I binding to human fibroblast monolayer cultures by insulinlike growth factor carrier proteins released to the incubation media.
Authors: M A De Vroede, L Y Tseng, P G Katsoyannis, S P Nissley, M M Rechler
Journal: Journal of Clinical Investigation (1986)

The relative contributions of type I and type II insulinlike growth factor (IGF) receptors and IGF carrier proteins to the binding of IGF-I tracer to cultured human fibroblasts were determined in competitive binding experiments that used unlabeled insulin and synthetic insulin-IGF-I hybrid molecules containing the A chain of insulin and the B domain of IGF-I. Whereas insulin binds only to type I IGF receptors, the B-IGF-I hybrids bind to type I receptors and IGF carrier proteins but not to type II receptors. In suspended human fibroblasts, IGF-I tracer binds predominantly to type I IGF receptors (inhibition by IGF-I much greater than insulin greater than B-IGF-I hybrid molecules). By contrast, in fibroblast monolayers, IGF-I binding was minimally inhibited by insulin or hybrid molecules, suggesting predominant binding to the type II IGF receptor. The type I receptor appears to be masked on fibroblast monolayers, and to require suspension or detergent solubilization of the cells to be demonstrated. In the course of the monolayers binding experiments, we noted that low concentrations of unlabeled IGF-I (5-10 ng/ml) or B-IGF-I hybrids (100 ng/ml) paradoxically increased IGF-I tracer binding up to twofold. We postulated that during the binding incubation (5 h, 15 degrees C), IGF-I tracer partitioned between binding sites on the cell surface and IGF carrier proteins released to the incubation media. Preferential occupancy of binding sites in the media by unlabeled ligand increased the tracer available to bind to the cells. In support of this hypothesis, carrier proteins were demonstrated in the media at the end of the binding incubation with fibroblast monolayers, and the concentration of unsaturated binding sites in the media correlated inversely with tracer binding to the cells. Thus carrier proteins released to the media during the binding incubation modulate the binding of IGF-I tracer to cell receptors, suggesting that the carrier proteins may play an important role in regulating cellular responsiveness to the IGFs.
Determinants of Progression of Microalbuminuria in Patients With NIDDM: A prospective study
Authors: Yvo M Smulders, Melina Rakic, Coen D A Stehouwer, Rob N M Weijers, Ed H Slaats, Joseph Silberbusch
Journal: Diabetes Care (1997)

OBJECTIVE To assess the degree of interindividual variation in the rate of progression of microalbuminuria and to identify determinants of progression of microalbuminuria in patients with NIDDM. RESEARCH DESIGN AND METHODS In a prospective cohort study, 58 microalbuminuric NIDDM patients were followed for a period of at least 24 months. During this period, the level of microalbuminuria in these patients was assessed in triplicate 24-h urine samples on at least four separate visits. All patients had stable metabolic control and controlled blood pressure during follow-up. Microalbuminuria was defined as an albumin-to-creatinine ratio in 24-h urine of between 3 and 30 mg/mmol. The individual rates of progression of microalbuminuria were calculated from linear regression analysis. At baseline, the following data were collected for all patients: age, sex, ethnicity, time since diagnosis of NIDDM, smoking habits, drug use, blood pressure, BMI, HbA1c, serum creatinine, cholesterol, triglyceride, and HDL cholesterol concentrations. RESULTS Microalbuminuria was found to progress linearly in time. Considerable differences in rates of progression of microalbuminuria were found, the absolute yearly change in albumin-to-creatinine ratio ranging from −5.2 to 12.9 mg/mmol. In bivariate analyses, serum triglyceride concentration, use of ACE inhibitors, mean arterial blood pressure, HDL cholesterol, and time since diagnosis of NIDDM correlated with progression of microalbuminuria (P ≤ 0.05). In stepwise multiple regression analysis, a high triglyceride-to–HDL cholesterol ratio at baseline (P = 0.006) and the use of ACE inhibitors (P = 0.007) were identified as the only independent predictors of progression of microalbuminuria. CONCLUSIONS The rate of progression of microalbuminuria in NIDDM differs considerably between subjects. Diabetic dyslipidemia (high serum triglyceride and low HDL cholesterol) is a predictor of more rapid progression of microalbuminuria in patients with well-controlled blood pressure.
The Indications for Transfusion of Freshly Drawn Blood
Authors: Harold A. Oberman
Journal: JAMA (1967)

The use of freshly drawn blood for transfusion should be justified by the clinical and laboratory findings manifested by the patient in relation to the known effects of storage on blood. Empirical administration of this product is wasteful, for it depletes the available donor pool and interferes with blood-bank inventory. A review of a variety of clinical situations that frequently occasion requests for freshly drawn blood indicates that most can be treated optimally with specific blood components, relatively fresh blood, or, in some instances, blood of any storage age.
B‐cell chronic lymphocytic leukaemia: Prognostic value of the immunophenotype and the clinico‐haematological features
Authors: Alberto Orfao, Marcos Gonzalez, J. San Fernando Miguel, Agustin Rios, M. Consuelo Canizo, Jose Hernandez, M. Lourdes Maricato, Antonio Lopez Borrasca
Journal: American Journal of Hematology (1989)

Abstract Sixty‐two previously untreated patients with B‐cell chronic lymphocytic leukaemia were analysed to study the prognostic value of both the immunologic phenotype and the clinicobiologic characteristics. Univariate studies showed that none of the immunological markers analysed, sheep‐rosette, mouse‐rosette, slg, and HLA/DR, CD20, FMC7, CD5, and CD9 antigens, had a significant influence on survival. On the other hand, several clinical and haematological characteristics were identified as being associated with survival: 1) clinical features—presence of lymphadenopathies ( P &lt; .05) and hepatomegaly and/or splenomegaly ( P &lt; .04); 2) haematologic parameters—presence of anaemia and/or thrombopenia ( P &lt; .05), the absolute peripheral blood lymphocyte count ( P &lt; .03), and the presence of hypogammaglobulinemia ( P &lt; .08); 3) biochemical parameters—serum uric acid ( P &lt; .03); and 4) bone marrow histopathological features—biopsy pattern ( P &lt; .04) and the percentage of lymphocytes in bone marrow aspirate ( P &lt; .03). Both the Rai staging and the International Workshop on CLL staging systems were effective in identifying groups of patients with significantly different prognoses ( P &lt; .05). Multivariate regression analysis demonstrated that the combination of three clinicopathologic characteristics (bone marrow histopathologic pattern, absolute peripheral blood lymphocyte count, and the presence or not of hypogammaglobulinaemia) had the strongest predictive relationship with survival time. In summary, our findings show that the clinicobiological and anatomopathologic parameters have much more prognostic relevance than the immunological markers analysed in the present study.
A New Percussion Technic
Authors: FRANK SMITHIES
Journal: Annals of Internal Medicine (1932)

Article1 October 1932A New Percussion TechnicFRANK SMITHIES, SC. D., M.D., M.A.C.P.FRANK SMITHIES, SC. D., M.D., M.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-6-4-482 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptDuring the World War, when a member of a "draft-board team", the writer was, of necessity, compelled to examine physically a great number of candidates over a period of many months. In percussing thoraces, particularly by the ordinary mid-finger of one hand (hammer) to mid-finger of the other hand (pleximeter) method, a few hours' work resulted in a very sore dorsal surface of the pleximeter finger, even when the nail on the "hammer finger" was kept short, shaped broadly and smoothed by means of the emery stick. The joint of the hammer finger not rarely became swollen and painful and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: FRANK SMITHIES, SC. D., M.D., M.A.C.P.Affiliations: Chicago, IllinoisReceived for publication, March 8, 1932. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1932Volume 6, Issue 4Page: 482-484KeywordsThorax ePublished: 1 December 2008 Issue Published: 1 October 1932 PDF downloadLoading ...
Auto-immune Haemolytic Anaemia and Thrombocytopenia Complicating Infectious Mononucleosis
Authors: D. S. Smith, J. D. Abell, I. P. Cast
Journal: BMJ (1963)

ITISOURNALthe isolation was made in an established focus of kala-azar.Three of the volunteers were susceptible to kala-azar; one had been immunized previously.Two of the susceptible subjects have developed kalaazar, while the third still has active leishmanial nodules in his skin; the immunized subject showed a modified reaction of immunity to the inoculation, and has remained healthy.The sandfly strain of Leishmania is thus identified as L. donovani; it is suggested that P. martini is a vector of kala-azar in Kenya.The importance of this study in the epidemiology and control of kala-azar in Kenya is briefly discussed.
Involvement of tachykinin receptors (NK1 and NK2) in sodium metabisulfite-induced airway effects.
Authors: T Sakamoto, H Tsukagoshi, P J Barnes, K F Chung
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We have investigated the effects of CP-96,345 and SR-48968, new nonpeptide (neurokinin) NK1 and NK2 receptor antagonists, respectively, against bronchoconstriction and airway microvascular leakage induced by inhaled sodium metabisulfite (MBS) in anesthetized guinea pigs. Lung resistance (RL) was measured for 6 min after challenge, followed by measurement of extravasation of Evans blue dye into airway tissues, used as an index of airway microvascular leakage. MBS (80 mM, 30 breaths) caused a significant increase in RL and leakage of dye at all airway levels. CP-96,345 (2 mg/kg, intravenous) but not SR-48968 (1.5 mg/kg, intravenous) significantly inhibited the leakage of dye at all airway levels except for trachea. Each antagonist inhibited significantly the maximal increase in RL. The combination had a significant additive effect against the bronchoconstriction, when compared with SR-48968 alone, and significantly inhibited the leakage of dye at the same airway levels as CP-96,345. We conclude that bronchoconstriction induced by inhaled MBS is, at least partly, mediated by activation of both NK1 and NK2 receptors, and the airway microvascular leakage by NK1 receptor stimulation alone.
Plasmacytoid dendritic cells induce NK cell–dependent, tumor antigen–specific T cell cross-priming and tumor regression in mice
Authors: Chengwen Liu, Yanyan Lou, Gregory Lizée, Hong Qin, Shujuan Liu, Brian Rabinovich, Grace J. Kim, Yi-Hong Wang, Yang Ye, Andrew G. Sikora, Willem W. Overwijk, Yong-Jun Liu, Gang Wang, Patrick Hwu
Journal: Journal of Clinical Investigation (2008)

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-γ production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8+ T cells.