tbuckley/cabot-search huggingface dataset:
PREPARATION AND ANTIGENICITY OF M PROTEIN RELEASED FROM GROUP A, TYPE 1 STREPTOCOCCAL CELL WALLS BY PHAGE-ASSOCIATED LYSIN
Authors: Fred S. Kantor, Roger M. Cole
Journal: The Journal of Experimental Medicine (1960)

The lysis of Group A type 1 streptococcal cell walls by phage-associated lysin has been described. In the preparation of lysin, a new semisynthetic non-protein media to support growth of the propagating strain of Group C streptococci was employed. Following lysis of the cell walls, the resulting digest was partially purified by ion-exchange chromatography and ammonium sulfate precipitation. In addition to M protein, the resulting preparation (called lysin M protein) contained the group-specific carbohydrate and the T protein—but did not contain antigens, detectable by precipitin tests, which cross-reacted with absorbed heterologous group or type antisera. Capillary precipitin reactions between the lysin M protein and type-specific antiserum did not occur in the presence of high ionic strength buffers; these buffers did not similarly affect precipitin reactions of acid M protein. Type 1 lysin M protein is shown to be a good antigen. A total of 1.5 mg. injected intradermally in saline produced bactericidal antibody in eight of nine rabbits; when injected in adjuvant in one rabbit, protective serum antibodies developed. Streptococci grown in sera from seven of nine rabbits immunized with lysin M protein demonstrated significantly longer chains than when grown in normal rabbit serum. Antibody as demonstrated by each of these three tests was shown to be type-specific. No local or systemic toxicity was noted following intradermal injection in rabbits of lysin M protein.
Genomics and Proteomics of Bone Cancer
Authors: Aaron G. Marguiles, V. Suzanne Klimberg, Sudeepa Bhattacharrya, Dana Gaddy, Larry J. Suva
Journal: Clinical Cancer Research (2006)

Abstract Although the control of bone metastasis has been the focus of intensive investigation, relatively little is known about the molecular mechanisms that regulate or predict the process, even though widespread skeletal dissemination is an important step in the progression of many tumors. As a result, understanding the complex interactions contributing to the metastatic behavior of tumor cells is essential for the development of effective therapies. Using a state-of-the-art combination of gene expression profiling and functional annotation of human tumor cells, and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of patient serum, we have shown that changes in tumor biochemistry correlate with disease progression and help to define the aggressive tumor phenotype. Based on these approaches, it is apparent that the metastatic phenotype of tumor cells is extremely complex. The identification of the phenotype of tumor cells has benefited greatly from the application of gene expression profiling (microarray analysis). This technology has been used by many investigators to identify changes in gene expression and cytokine and growth factor elaboration (such as interleukin 8). The tumor phenotype(s) presumably also include changes in the cell surface carbohydrate profile (via altered glycosyltransferase expression) and heparan sulfate expression (via increased heparanase activity), to name but a few. These specific alterations in gene expression, identified by functional annotation of accumulated microarray data, have been validated using a variety of approaches. Collectively, the data described here suggest that each of these activities is associated with distinct aspects of the aggressive tumor cell phenotype. Collectively, the data suggest that multiple factors constitute the complex phenotype of metastatic tumor cells. In particular, the differences observed in gene expression profiles and serum protein biomarkers play a critical role in defining the mechanisms responsible for bone-specific colonization and growth of tumors in bone. Future studies will identify the mechanisms that participate in the formation of secondary tumor growths of cancers in bone.
Transplacental Teratogenic and Carcinogenic Effects in Rabbits Chronically Treated With &lt;italic&gt;N&lt;/italic&gt;-Ethyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: R R Fox, H Meier, R Pottathil, H G Bedigian
Journal: JNCI Journal of the National Cancer Institute (1980)

Pregnant rabbits of two partially inbred strains, WH/J and IIIVO/J, were given ten consecutive daily ip injections of 10 mg N-ethyl-N-nitrosourea (ENU)/kg dissolved in trioctanoin starting on either day 10, 15, or 18 of gestation. Of 7 WH/J progeny weaned, 3 developed primary renal tumors at 6.8±0.6 months of age (mean ± SE). Similarly, of 12 IIIVO/J progeny weaned, 10 developed primary renal tumors at 6.3±0.6 months of age (mean ± SE); in addition, 1 fibroblastic osteosarcoma and 5 neurofibromas, some associated with neurilemma cysts, were observed. Renal tumors were nephroblastomas, which appeared to develop within small renal cortical cysts. The frequency of tumor induction for each strain was similar to that in our previous experiments with acute administration of ENU and ethylurea plus NaNO2, but the latency period (6.4±0.5 mo) was almost doubled. In addition, chronic treatment of ENU induced teratogenic effects. In a number of these progeny, a disproportionate stunting or miniaturization was evident, the frequency of which increased with the age of the treated fetuses. In contrast, holes were found in the parietal bones at birth, but with a frequency that decreased with increasing fetal age at time of treatment. No teratogenic effects were observed in the controls.
Long-Term Follow-Up of Autotransplantation Trials for Multiple Myeloma: Update of Protocols Conducted by the Intergroupe Francophone du Myelome, Southwest Oncology Group, and University of Arkansas for Medical Sciences
Authors: Bart Barlogie, Michel Attal, John Crowley, Frits van Rhee, Jackie Szymonifka, Philippe Moreau, Brian G.M. Durie, Jean-Luc Harousseau
Journal: Journal of Clinical Oncology (2010)

The purpose of this study was to update outcomes of autotransplantation trials for myeloma conducted by the Intergroupe Francophone du Myelome (IFM), the Southwest Oncology Group, and the University of Arkansas for Medical Sciences (Total Therapy [TT]).
Pulmonary function and complications following chemotherapy and stem cell support in breast cancer
Authors: F. Fanfulla, P. Pedrazzoli, G.A Da Prada, C Bruschi, E Dacosto, A Zambelli, G.R della Cuna, C Rampulla
Journal: European Respiratory Journal (2000)

Pulmonary complications are frequent in patients treated with high-dose chemotherapy and autologous bone marrow transplantation for breast cancer or other solid tumours. This study analyses the development of lung toxicity, changes in respiratory function and occurrence of clinical symptoms in a group of 24 patients (mean age 46+/-7 yrs) who underwent high-dose sequential chemotherapy (HDS) with autologous peripheral blood stem cell (PBSC) support for high risk breast cancer. Clinical examination, chest radiography and lung function tests were performed before the HDS and 1 and 3 months following transplantation. Only one patient developed acute interstitial pulmonary disease which resolved after prednisone therapy. No patients developed infectious complications after transplantation. Baseline respiratory function was normal for most of the parameters. Only lung diffusing capacity of the lung for carbon monoxide (TL,CO) and maximal inspiratory pressure were below the normal range. Following PBSC transplantation only one patient had an altered vital capacity while 72.3% of patients had reduced TL,CO values at 1 month and 54.5% at 3 months after transplantation. Maximal expiratory flow at 25% forced vital capacity, TL,CO and maximal expiratory pres-sure were significantly reduced after 1 month but recovered slightly by 3 months. Arterial oxygen tension between baseline and both follow-up evaluations declined significantly in patients seropositive for human cytomegalovirus. It is concluded that this high-dose sequential chemotherapy regimen is acceptably safe since no pulmonary related mortality or respiratory infectious complications were observed. The only lung function alteration induced was an isolated diffusing capacity of the lung for carbon monoxide impairment, clinically negligible and partially recovered within 3 months.
Akt SUMOylation Regulates Cell Proliferation and Tumorigenesis
Authors: Rong Li, Jie Wei, Cong Jiang, Dongmei Liu, Lu Deng, Kai Zhang, Ping Wang
Journal: Cancer Research (2013)

Abstract Proto-oncogene Akt plays essential roles in cell proliferation and tumorigenesis. Full activation of Akt is regulated by phosphorylation, ubiquitination, and acetylation. Here we report that SUMOylation of Akt is a novel mechanism for its activation. Systematically analyzing the role of lysine residues in Akt activation revealed that K276, which is located in a SUMOylation consensus motif, is essential for Akt activation. Ectopic or endogenous Akt1 could be modified by SUMOylation. RNA interference–mediated silencing of UBC9 reduced Akt SUMOylation, which was promoted by SUMO E3 ligase PIAS1 and reversed by the SUMO-specific protease SENP1. Although multiple sites on Akt could be SUMOylated, K276 was identified as a major SUMO acceptor site. K276R or E278A mutation reduced SUMOylation of Akt but had little effect on its ubiquitination. Strikingly, these mutations also completely abolished Akt kinase activity. In support of these results, we found that expression of PIAS1 and SUMO1 increased Akt activity, whereas expression of SENP1 reduced Akt1 activity. Interestingly, the cancer-derived mutant E17K in Akt1 that occurs in various cancers was more efficiently SUMOylated than wild-type Akt. Moreover, SUMOylation loss dramatically reduced Akt1 E17K–mediated cell proliferation, cell migration, and tumorigenesis. Collectively, our findings establish that Akt SUMOylation provides a novel regulatory mechanism for activating Akt function. Cancer Res; 73(18); 5742–53. ©2013 AACR.
Guidelines for the Management of Adults with Community-acquired Pneumonia
Authors: Michael S. Niederman, Lionel A. Mandell, Antonio Anzueto, John B. Bass, William A. Broughton, G. Douglas Campbell, Nathan Dean, Thomas File, Michael J. Fine, Peter A. Gross, Fernando Martinez, Thomas J. Marrie, Joseph F. Plouffe, Julio Ramirez, George A. Sarosi, Antonio Torres, Robert Wilson, Victor L. Yu
Journal: American Journal of Respiratory and Critical Care Medicine (2001)
Targeted treatments in colorectal cancer: state of the art and future perspectives
Authors: D. Arnold, T. Seufferlein
Journal: Gut (2010)

Targeted treatments have generated a lot of hope and hype in the treatment of gastrointestinal tumours. Indeed, the introduction of targeted treatments particularly for colorectal cancer has resulted in substantial improvements in tumour response and progression-free survival of patients. However, it is not fully understood how these agents act in patients, and the preclinical models are not appropriate to predict clinical efficacy. Here the current state of targeted treatments in colorectal cancer is reviewed, focusing on antiepidermal growth factor receptor (EGFR) and antiangiogenic strategies, describing how these agents fit into the therapeutic algorithm of this disease and discussing current understanding of the mechanism of action, biomarkers as well as future therapeutic strategies targeting multiple signalling pathways in colorectal cancer.
Diagnostic tests for Helicobacter pylori Reply
Authors: J KOUNTOURAS, R P WALT
Journal: Gut (1998)

Editor,—I read the article on the comparison of serum, salivary, and rapid whole blood diagnostic tests for Helicobacter pylori and their validation against endoscopy based tests, by Reilly et al ( Gut 1997; 40 :454–8) with considerable interest because, in addition to other comments, they would not recommend the routine use of salivary antibodies as a method of choosing appropriate endoscopy in H pylori positive patients being considered for this test.

Our results on patients with peptic ulcer, published in 1996,1 suggest that saliva urease testing seems to be the preferred method for screening purposes and for following the effectiveness of eradication therapy for H pylori infection. Indeed, we followed two groups of patients with peptic ulcer treated for H pylori infection to see, mainly, whether monitoring treatment by the non-endoscopic means of a urease test and serology was informative. All patients were treated with amoxycillin and lansoprazole and followed mainly using the saliva urease test (CLO, Delta West) and serology (IgG anti- …
Monocyte-Directed RNAi Targeting CCR2 Improves Infarct Healing in Atherosclerosis-Prone Mice
Authors: Maulik D. Majmudar, Edmund J. Keliher, Timo Heidt, Florian Leuschner, Jessica Truelove, Brena F. Sena, Rostic Gorbatov, Yoshiko Iwamoto, Partha Dutta, Gregory Wojtkiewicz, Gabriel Courties, Matt Sebas, Anna Borodovsky, Kevin Fitzgerald, Marc W. Nolte, Gerhard Dickneite, John W. Chen, Daniel G. Anderson, Filip K. Swirski, Ralph Weissleder, Matthias Nahrendorf
Journal: Circulation (2013)

Background— Exaggerated and prolonged inflammation after myocardial infarction (MI) accelerates left ventricular remodeling. Inflammatory pathways may present a therapeutic target to prevent post-MI heart failure. However, the appropriate magnitude and timing of interventions are largely unknown, in part because noninvasive monitoring tools are lacking. Here, we used nanoparticle-facilitated silencing of CCR2, the chemokine receptor that governs inflammatory Ly-6C high monocyte subset traffic, to reduce infarct inflammation in apolipoprotein E–deficient (apoE −/− ) mice after MI. We used dual-target positron emission tomography/magnetic resonance imaging of transglutaminase factor XIII (FXIII) and myeloperoxidase (MPO) activity to monitor how monocyte subset–targeted RNAi altered infarct inflammation and healing. Methods and Results— Flow cytometry, gene expression analysis, and histology revealed reduced monocyte numbers and enhanced resolution of inflammation in infarcted hearts of apoE −/− mice that were treated with nanoparticle-encapsulated siRNA. To follow extracellular matrix cross-linking noninvasively, we developed a fluorine-18–labeled positron emission tomography agent ( 18 F-FXIII). Recruitment of MPO-rich inflammatory leukocytes was imaged with a molecular magnetic resonance imaging sensor of MPO activity (MPO-Gd). Positron emission tomography/magnetic resonance imaging detected anti-inflammatory effects of intravenous nanoparticle-facilitated siRNA therapy (75% decrease of MPO-Gd signal; P &lt;0.05), whereas 18 F-FXIII positron emission tomography reflected unimpeded matrix cross-linking in the infarct. Silencing of CCR2 during the first week after MI improved ejection fraction on day 21 after MI from 29% to 35% ( P &lt;0.05). Conclusion— CCR2-targeted RNAi reduced recruitment of Ly-6C high monocytes, attenuated infarct inflammation, and curbed post-MI left ventricular remodeling.
British Thoracic Society Winter Meeting 2000
Authors: L Hosking
Journal: Thorax (2001)

The weather and the transport crisis threatened the British Thoracic Society Millennium Winter Meeting but, despite these problems, more than 1500 delegates attended.A wide range of topics in respiratory medicine was covered in the three days of the meeting.There were more overseas "experts" presenting than at previous meetings, and a "top and tail" or overview format was introduced to several of the slide and poster sessions.
Early childhood weight status in relation to asthma development in high-risk children
Authors: Zhumin Zhang, HuiChuan J. Lai, Kathy A. Roberg, Ronald E. Gangnon, Michael D. Evans, Elizabeth L. Anderson, Tressa E. Pappas, Douglas F. DaSilva, Christopher J. Tisler, Lisa P. Salazar, James E. Gern, Robert F. Lemanske
Journal: Journal of Allergy and Clinical Immunology (2010)
TLR4 signaling potentiates airway secretion from the swine submucosal gland via NO/cGMP/cGK pathway
Authors: Koji Murakami, Tsutomu Tamada, Masayuki Nara, Soshi Muramatsu, Toshiaki Kikuchi, Masahiko Kanehira, Masahito Ebina
Journal: European Respiratory Journal (2012)

[RATIONALE] Airway secretion plays an important role in the airway defense as a part of innate immunity. A major fraction of the airway fluids appears to be derived from submucosal gland in response to ACh. Toll-like receptor 4 (TLR4) recognizes gram-negative bacteria and activates the innate immune systems. However, the biological role of TLR4 in the airway secretion is not well understood.  [METHODS] Freshly isolated swine tracheal submucosal gland cells were investigated their secretory activities as ionic currents by applying a patch-clamp technique. LPS was used as a potent TLR4 ligand. The expression of TLR4 was estimated by both the immunofluorescent staining and RT-PCR. The involvement of NO/cGMP/cGMP-dependent protein kinase (cGK) pathway was investigated by applying both the NOS and cGK inhibitors. The synthesis of endogenous NO was estimated by an intracellular NO indicator, DAF-2DA.  [RESULTS] LPS significantly potentiated the ACh-evoked ionic currents. This potentiating effect was completely abolished by the pretreatment of anti-TLR4 antibody or TLR4 antagonist. The immunofluorescent staining and RT-PCR revealed the abundant expression of TLR4 on tracheal submucosal glands. Two different inhibitors of each NOS and cGK completely abolished the LPS-induced potentiating effect, respectively. LPS further increased the ACh-induced synthesis of NO.  [CONCLUSIONS] Our studies revealed that TLR4 signaling could potentiate the electrolyte and water secretions from tracheal submucosal glands via the activation of NO/cGMP/cGK pathway. These findings suggest that TLR4 takes part in the airway mucosal innate immune systems as one of important pathogen-specific secretagogue.
Renin and Aldosterone Secretion in Man as Influenced by Changes in Electrolyte Balance and Blood Volume
Authors: MARCIA B. BULL, ROBERT S. HILLMAN, PAUL J. CANNON, JOHN H. LARAGH
Journal: Circulation Research (1970)

In six normal volunteers maintained on a constant dietary intake, serial studies were made of plasma renin activity, blood volume, aldosterone secretion and sodium balance, first following dietary and diuretic-induced depletion of sodium and blood volume, then following a period of sodium repletion during a maintained reduction in blood volume, and finally after blood volume repletion. In the first phase, during which depletion of blood volume paralleled sodium depletion, renin and aldosterone secretion were both increased. Under the circumstances of a subsequent study period, however, it was possible to separate the effects of sodium depletion from those of reduction in total blood volume. In this period, the administration of sodium chloride was associated with an increased urinary sodium excretion and a marked suppression of plasma renin and aldosterone secretion at a time when total blood volumes were maintained below control values by repeated plasmapheresis and phlebotomy. This sodium-dependent suppression of renin and aldosterone secretion may have been mediated by an expansion in extravascular fluid volume(s). However, the observed effects are perhaps better explained in terms of an induced change in intrarenal tubular sodium transport. The parallelism observed between the changes in renin and aldosterone secretion suggests that under the conditions of these studies renin plays a major role in regulating aldosterone secretion.
Coagulation disorders and hemostasis in liver disease: Pathophysiology and critical assessment of current management
Authors: Stephen H. Caldwell, Maureane Hoffman, Ton Lisman, B. Gail Macik, Patrick G. Northup, K. Rajender Reddy, Armando Tripodi, Arun J. Sanyal, Nathan Bass, Andres T. Blei, Michael Fallon, Don Gabriel, Pere Gines, Peter Grant, Kris Kowdley, Samuel Lee, Santiago Munoz, Ian Wanless, Abdullah M. Al-Osaimi, Carl I. Berg, Rasheed Balogun, Thomas P Bleck, David L. Bogdonoff, Andrew Martoff, Paul Mintz, Timothy L. Pruett
Journal: Hepatology (2006)

Normal coagulation has classically been conceptualized as a Y-shaped pathway, with distinct "intrinsic" and "extrinsic" components initiated by factor XII or factor VIIa/tissue factor, respectively, and converging in a "common" pathway at the level of the FXa/FVa (prothrombinase) complex. Until recently, the lack of an established alternative concept of hemostasis has meant that most physicians view the "cascade" as a model of physiology. This view has been reinforced by the fact that screening coagulation tests (APTT, prothrombin time--INR) are often used as though they are generally predictive of clinical bleeding. The shortcomings of this older model of normal coagulation are nowhere more apparent than in its clinical application to the complex coagulation disorders of acute and chronic liver disease. In this condition, the clotting cascade is heavily influenced by numerous currents and counter-currents resulting in a mixture of pro- and anticoagulant forces that are themselves further subject to change with altered physiological stress such as super-imposed infection or renal failure. This report represents a summary of a recent multidisciplinary symposium held in Charlottesville, VA. We present an overview of the coagulation system in liver disease with emphasis on the limitations of the current clinical paradigm and the need for a critical re-evaluation of the current tenets governing clinical practice. With the realization that there is often limited or conflicting data, we have attempted to represent diverse opinion and experience from the perspectives of both hepatology and hematology beginning with a brief update on the physiology of normal coagulation.
Nutrition support for elite athletes: lessons learnt from the 2006 Commonwealth Games
Authors: Fiona E Pelly
Journal: British Journal of Sports Medicine (2010)

Provision of a nutrition support service at elite level competition can assist athletes to make informed food selection at a critical time in their sporting career. Research conducted at the Sydney 2000 Olympic Games revealed that nutrition labelling and access to dietitians was rated highly and widely used by athletes across a range of countries, cultures and sports. The aim of this study was to evaluate a comprehensive nutrition support service within the athletes' village of the Melbourne 2006 Commonwealth Games. The nutrition services available included nutrition labelling of menu items, fact sheets, individual or group dietetic consultations and a request service to cater for athletes with special dietary requirements. Dietitians kept detailed records of each occasion of service from the week prior to until the completion of competition. At the end of each consultation, clients were invited to complete an evaluation of the service provided. In addition, a questionnaire was distributed randomly to patrons in the dining hall. The majority of athletes (67%) rated nutrition information as being very important or essential in determining their food choice, with 87% of athletes using the nutrition labelling at least some of the time. Nearly 60% of respondents said that the menu met their special dietary needs, supported by the small number (n=8) of requests requiring specialised catering. Evaluation of the nutrition support service confirmed its beneficial role in supporting the needs of athletes at elite level competition but also highlighted areas which could be improved for future games.