tbuckley/cabot-search huggingface dataset:
Novel Role for PDEF in Epithelial Cell Migration and Invasion
Authors: Ruwanthi N. Gunawardane, Dennis C. Sgroi, Carolyn N. Wrobel, Eugene Koh, George Q. Daley, Joan S. Brugge
Journal: Cancer Research (2005)

Abstract Cell migration and invasion are two critical cellular processes that are often deregulated during tumorigenesis. To identify factors that contribute to oncogenic progression by stimulating cell migration, we conducted a powerful retroviral based migration screen using an MCF7 cDNA library and the immortalized human breast epithelial cell line MCF-10A. We identified prostate derived Ets factor (PDEF), an Ets transcription factor that is overexpressed in both prostate and breast carcinoma, as a candidate promigratory gene from this screen. Whereas PDEF induced limited motility of MCF-10A cells, coexpression of PDEF with the receptor tyrosine kinases (RTK) ErbB2 and colony-stimulating factor receptor (CSF-1R)/CSF-1 significantly enhanced MCF-10A motility. Furthermore, cells coexpressing PDEF with either ErbB2 or CSF-1R/CSF-1 induced a dramatic invasive phenotype in three-dimensional cultures. Constitutive activation of the extracellular signal–regulated kinase (ERK) pathway also enhanced PDEF-induced motility and invasion, suggesting that activation of the ERK/mitogen-activated protein kinase by ErbB2 and CSF-1R/CSF-1 can cooperate with PDEF to promote motility and invasion. Furthermore, PDEF promoted anchorage-independent growth of ErbB2 and CSF-1R/CSF-1–expressing cells. Using laser capture microdissection, we also found that PDEF mRNA is overexpressed in breast tumor epithelia throughout tumor progression. Taken together, these findings suggest that the transcription factor PDEF may play an important role in breast tumorigenesis and that PDEF overexpression may be particularly significant in tumors that exhibit activation of oncogenic RTKs such as ErbB2 and CSF-1R. (Cancer Res 2005; 65(24): 11572-80)
Hemorrhagic Thrombocythemia
Authors: William J. Hall
Journal: JAMA (1965)

EVEN BEFORE Nygaard's and Brown's inclusion of a patient with thrombocytosis in their series of five patients with  thrombophilia in 1937, 1 scattered reports of patients with thrombohemorrhagic phenomena and increased numbers of circulating platelets had appeared in the English and foreign medical literature under such names as piastrinemia, primary thrombocythemia, essential thrombocythemia, hemorrhagic thrombocythemia, megakaryocytic leukemia, hyperthrombocytic myelosis, and essential thrombophilia. 2   The present report describes an instance of hemorrhagic thrombocythemia studied at the Eugene Talmadge Memorial Hospital of the Medical College of Georgia. It is the first report, to the author's knowledge, to include definition of patient karyotype. The reader is referred to the reviews of hemorrhagic thrombocythemia by Ozer et al 2 and Gunz. 3   Report of a Case  A 52-year-old Negro woman (ETMH 018-900) was admitted to the Eugene Talmadge Memorial Hospital for the sixth time on Jan 30, 1964, with the complaint of abdominal
Endoscopic Retrograde Cholangiopancreatography in the Orthotopic Liver Transplant Patient
Authors: M. F. Catalano, J. Van Dam, M. V. Sivak, Jr.
Journal: Endoscopy (1995)

Background and Study Aims: Diagnostic imaging of the biliary tract is often required in liver transplant reciplents, preoperatively to assess extent of biliary tract disease and postoperatively in patients with a suspected biliary complication due to an abnormal postoperative course.
Carisoprodol in Cerebral Palsy
Authors: G. E. Woods
Journal: BMJ (1964)

SIR,-In the article on carisoprodol under the heading of " To-day's Drugs " (23 May, p. 1363) it is stated that there have been no published reports on the use of carisoprodol in cerebral palsy in Great Britain.I would like to mention that in 1962 I published two articles on a preliminary trial and a double-blind trial of carisoprodol in cerebral palsy.' 2 Although the trials were not completely convincing they did suggest that the drug was responsible for an improvement in certain cases of severe athetosis and in some cases of spastic diplegia.The drug is worth trying in cases of athetosis with marked extensor spasm and in cases of spasticity where there is an element of superadded emotional tension.I understand that this is the impression gained after use of this drug in other centres here and abroad.-Iam, etc.,
Whole-Cell Protein Identification Using the Concept of Unique Peptides
Authors: Yupeng Zhao, Yen-Han Lin
Journal: Genomics Proteomics & Bioinformatics (2010)

Abstract A concept of unique peptides (CUP) was proposed and implemented to identify whole-cell proteins from tandem mass spectrometry (MS/MS) ion spectra. A unique peptide is defined as a peptide, irrespective of its length, that exists only in one protein of a proteome of interest, despite the fact that this peptide may appear more than once in the same protein. Integrating CUP, a two-step whole-cell protein identification strategy was developed to further increase the confidence of identified proteins. A dataset containing 40,243 MS/MS ion spectra of Saccharomyces cerevisiae and protein identification tools including Mascot and SEQUEST were used to illustrate the proposed concept and strategy. Without implementing CUP, the proteins identified by SEQUEST are 2.26 fold of those identified by Mascot. When CUP was applied, the proteins bearing unique peptides identified by SEQUEST are 3.89 fold of those identified by Mascot. By cross-comparing two sets of identified proteins, only 89 common proteins derived from CUP were found. The key discrepancy between identified proteins was resulted from the filtering criteria employed by each protein identification tool. According to the origin of peptides classified by CUP and the commonality of proteins recognized by protein identification tools, all identified proteins were cross-compared, resulting in four groups of proteins possessing different levels of assigned confidence.
Tuberculosis and the N.H.S. Act
Authors: H. Vallow
Journal: BMJ (1947)

JOURNAL693it, and the basic neglect.The opportunity which this chal- lenge presented came with the introduction of the National Health Service, which promised to every citizen the treatment he needed, but the opportunity was also a heavy responsibility for medicine.Even with present knowledge, if there were suffi- cient hospital beds and adequate treatment facilities the invalidism resulting from rheumnatism could be greatly lessened.
Haemophilus influenzae tenosynovitis.
Authors: S Bansal, C R Magnussen, R J Napodano
Journal: Annals of the Rheumatic Diseases (1979)

A case is reported of polytenosynovitis in a 31-year-old male during the course of a severe bacteraemic illness caused by Haemophilus influenzae type b. The clinical presentation was similar to tenosynovitis caused by bacterial or viral agents. As the management of the H. influenzae tenosynovitis would differ from that due to other causes, the addition of H. influenzae type b to a differential of tenosynovitis should be considered. Recognition and prompt treatment by appropriate antibiotics may be important to avoid suppurative complications affecting the tendons. As the pathophysiology of the tenosynovitis is not clear, careful bacteriological and immunological assessment must be obtained.
Molecular-based prediction of early recurrence in hepatocellular carcinoma
Authors: Yukinori Kurokawa, Ryo Matoba, Ichiro Takemasa, Hiroaki Nagano, Keizo Dono, Shoji Nakamori, Koji Umeshita, Masato Sakon, Noriko Ueno, Shigeyuki Oba, Shin Ishii, Kikuya Kato, Morito Monden
Journal: Journal of Hepatology (2004)
Lung Deposition and Cellular Uptake Behavior of Pathogen‐Mimicking Nanovaccines in the First 48 Hours
Authors: Kathleen A. Ross, Shannon L. Haughney, Latrisha K. Petersen, Paola Boggiatto, Michael J. Wannemuehler, Balaji Narasimhan
Journal: Advanced Healthcare Materials (2014)

Pulmonary immunization poses the unique challenge of balancing vaccine efficacy with minimizing inflammation in the respiratory tract. While previous studies have shown that mice immunized intranasally with F1‐V‐loaded polyanhydride nanoparticles are protected from a lethal challenge with Yersinia pestis , little is known about the initial interaction between the nanoparticles and immune cells following intranasal administration. Here, the deposition within the lung and internalization by phagocytic cells of polyanhydride nanovaccines encapsulating F1‐V are compared with that of soluble F1‐V alone or F1‐V adjuvanted with monophosphoryl lipid A (MPLA). Encapsulation of F1‐V into polyanhydride nanoparticles prolonged its presence while F1‐V administered with MPLA is undetectable within 48 h. The inflammation induced by the polyanhydride nanovaccine is mild compared with the marked inflammation induced by the MPLA‐adjuvanted F1‐V. Even though F1‐V delivered with saline is detected in the lung 48 h after administration, it is known that this regimen does not elicit a protective immune response. The prolonged F1‐V presence in the lung in concert with the mild inflammatory response provided by the nanovaccine provides new insights into the development of protective immune responses with a single intranasal dose.
Reply from Authors re: Marc C. Smaldone, Veda N. Giri, Robert G. Uzzo. Familial Clustering of Sporadic Kidney Cancer: Insufficient Evidence to Recommend Routine Screening in Unaffected Kin. Eur Urol 2011;60:994–5
Authors: Kari Hemminki, Hao Liu
Journal: European Urology (2011)
Fragile X Mental Retardation Protein Is Required for Synapse Elimination by the Activity-Dependent Transcription Factor MEF2
Authors: Brad E. Pfeiffer, Tong Zang, Julia R. Wilkerson, Makoto Taniguchi, Marina A. Maksimova, Laura N. Smith, Christopher W. Cowan, Kimberly M. Huber
Journal: Neuron (2010)
Are written responses to referrals acceptable?: Comprehensive referral letters are key to safe written advice
Authors: Abdullah Mohammed
Journal: BMJ (2004)

Physiotherapy compared with advice for low back painTargeting "physical factors" alone is not evidence based practice Editor-Frost et al's conclusion that "routine physiotherapy" based on physical factors was no more effective than one session of assessment and advice from a physiotherapist in the management of low back pain is not surprising. 1 But the defensive nature of the responses to this research is. 2 3 This defensiveness arises partly from the perceived rivalry between healthcare professions managing low back pain and the attention grabbing headlines used.In recent years the evidence base has highlighted that low back pain is a multifaceted phenomenon incorporating physical impairment, psychological distress, and social interruption.Thus the effective biopsychosocial management of low back pain should reflect its multifaceted nature and not just focus on the "physical factors," as was done by Frost et al.Being an evidence based practitioner should entail identifying and managing patients' risk factors because risk factors are clinical predictors of outcome and efforts to manage them may reduce the burden of low back pain for those who consult physiotherapists.Because of the recurrent nature of low back pain, talk of a "cure" is unrealistic.Thus the Physiotherapy Pain Association emphasises that patients should be taught skills to self manage their low back problem so that in the long term they are less likely to experience pain related disability and depression, thus improving their quality of life.Receiving passive treatments focusing on physical factors, which show only slight short term benefits, is not in the personal or economic interest of patients with low back pain.As is highlighted by the responses to the study by Frost et al, 3 beliefs about treatment preferences for low back pain vary across professions and can be traced to beliefs about the cause of the problem.
Splinting vs Surgery for Carpal Tunnel Syndrome
Authors: Ernest W. Johnson
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Developments in Lymphoid Cell Biology
Authors: D. P. Shreiner
Journal: JAMA (1975)

Leukemia and Lymphoma  edited by G. Hamilton Fairley, Ernst R. Jaffe, and Peter A. Miescher (Semin Hematol, vol 11, No. 1-2), 230 pp, with illus, $14.50, New York, Grune & Stratton, 1975.   Developments in Lymphoid Cell Biology attempts to review some recent developments in immunology. Nine contributors have written seven chapters on specific aspects of immunology. The subjects considered are the role of macrophages, lymphoid cells, and eosinophils in immune responses; a consideration of immunologic tolerance; lymphocyte transformation; transplantation; and the role of the lung in the immunologic system. This is not a good review of recent developments in immunology, but rather a specific consideration of certain developments in current research in this field. The role of the complement system, for example, is not considered. Certain subjects, such as the chapter on the lung, have little relevance to a treatise on lymphoid cells and immunology. Many chapters suffer from lack
S76 Proteinase 3 activity in sputum from alpha-1-antitrypsin deficient subjects
Authors: N. J. Sinden, M. Ungurs, R. Edgar, P. Bharadwa, R. A. Stockley
Journal: Thorax (2011)

<h3>Introduction</h3> Tissue destruction in emphysema is widely believed to result from an imbalance between serine proteinases and their inhibitors, the antiproteinases. Previous work has studied the role of neutrophil elastase (NE), but there are few studies of proteinase 3 (PR3). PR3 is released from activated neutrophils concurrently with NE, is more abundant than NE and has fewer airway inhibitors. PR3, unlike NE, is not inhibited by secretory leukoproteinase inhibitor (SLPI). Some studies that have reported “elastase” activity in airway secretions have potentially measured the combined activities of PR3 and NE. Our hypothesis is that PR3 plays a more important role in the tissue damage of emphysema than has previously been considered. <h3>Methods</h3> Twenty-eight clinically stable patients with α-1-antitrypsin deficiency (A1ATD) were selected with the PiZZ phenotype and chronic bronchitis. The mean age was 55.8 years and 82% were male. All subjects had full pulmonary function tests and quality of life scores as measured by the St George9s Respiratory Questionnaire (SGRQ). Spontaneously produced sputum was collected for microbiology, and the sol-phase was obtained by ultracentrifugation. PR3 and NE activities were measured in all of the samples using specific substrates. The following measurements were taken in a selection of samples; myeloperoxidase (MPO), interleukin (IL)-8, and leukotriene (LT)-B4. A selection of patients had CT densitometry performed. <h3>Results</h3> In the sample of patients studied, PR3 activity was detected in all of the sol-phase sputum samples (mean 323.90 nm, SEM 72.46) whereas NE activity was detected in only 6 of the samples (overall mean 196.42 nm, SEM 100.59). PR3 activity correlated with IL-8 concentration (p=0.004), NE activity (p=0.001) and total pathogenic bacterial load (p=0.001). There was no significant correlation with myeloperoxidase or LTB4 concentrations. PR3 activity correlated with SGRQ total score (p=0.001) but no correlation was found with lung function parameters or CT densitometry. <h3>Conclusion</h3> This pilot study is the first to directly measure PR3 activity in sol-phase sputum. We have shown that PR3 activity can be detected in A1ATD patients, and correlates with the chemoattractant IL-8, NE activity, pathogenic bacterial load and SGRQ total score. PR3 activity should be assessed when evaluating proteinase-mediated airway damage.
Diagnosis of Diseases of the Chest
Authors: Reginald E. Greene
Journal: JAMA (1978)

The early appearance of a second edition of this monumental text is a tribute to the energy of the authors. The first edition has become the standard reference for roentgenographic diagnosis of diseases of the chest. The inclusion of extensive pathological, clinical, and physiological material has also made it a favorite among specialists in pulmonary medicine. The great increase of the body of knowledge in chest disease that has occurred since the first edition prompted the second writing. A substantial number of additions and important revisions have been incorporated into this first volume of the new four-volume text. Unfortunately, the large mass of new material has considerably increased the size of the new text. Except for deletion of the tables of differential diagnosis, which will be incorporated into volume 4, the scope of volume 1 of the second edition is the same as that of the first edition. Each of
77. TLR and Myd88 Signaling Pathway Is Required for the Full Induction of Host Adaptive Immune Responses to Adenoviral Vectors and Transgenes
Authors: Zhe Zhang, Yan Zhi, Joanita M. Figueredo, Roberto Calcedo, James R. Miller, Guang-Ping Gao, James M. Wilson
Journal: Molecular Therapy (2006)

Adaptive immune responses including T cell and B cell responses to both backbones of adenoviral vectors as well as the transgenes were studied in TLR and MyD88 signaling deficient mice. C57/B6, MyD88 knockout (KO) or TLR2 (KO) mice were intramuscularly injected with Ad5 carrying SARS membrane protein Spike, the frequency of INF-γ producing CD8+ T cells in response to a dominant CD8+ epitope of Spike was significantly reduced in both KO mice compared to C57B6 mice (INF-γ intracellular staining assay); T cell proliferation in response to Ad5 particles (H3 Thymidine incorporation assay) was also attenuated as observed in MyD88 KO mice.
Oral antiplatelet agents clopidogrel and prasugrel for the prevention of cardiovascular events
Authors: G. Passacquale, A. Ferro
Journal: BMJ (2011)

#### Case scenario

A 68 year old man with hypertension, type 2 diabetes, and stable angina developed severe dyspepsia while taking aspirin. In accordance with the Joint British Societies 2 guidelines,1 his general practitioner changed the aspirin to clopidogrel 75 mg daily, with no recurrence of dyspepsia. The patient was also taking simvastatin, ramipril, metformin, and isosorbide mononitrate. Six months later he developed non-ST elevation myocardial infarction, requiring immediate insertion of a paclitaxel eluting stent. Three days later he was discharged taking prasugrel 10 mg daily (in place of clopidogrel) to continue for one year plus aspirin 75 mg daily, in addition to his other medications. He was also started on omeprazole 40 mg daily owing to his history of aspirin induced dyspepsia.

Clopidogrel and prasugrel belong to the thienopyridine family of oral antiplatelet agents and are used for cardiovascular prophylaxis. As second and third generation thienopyridines respectively, they differ in chemical structure and metabolism (figure⇓). However, both are prodrugs, converted in vivo to active metabolites that selectively and irreversibly bind the purinergic receptor P2Y12 (receptor for adenosine diphosphate (ADP)) on platelets, thus preventing ADP dependent platelet activation.2 



Pathways of metabolism for clopidogrel and prasugrel. Their metabolism is a two step process, with production of an intermediate metabolite and subsequent conversion to the active compound. For clopidogrel, this process is entirely mediated by hepatic cytochrome P450 enzymes, whereas prasugrel is initially rapidly hydrolysed by intestinal esterase (carboxylesterase 2 (hCE2)) then metabolised further by cytochrome P450 to the active molecule. Therefore, prasugrel is less dependent than clopidogrel on hepatic cytochrome P450 for its activation, resulting in the formation of more active metabolite, faster onset of action, and higher degree of in vivo platelet inhibition.3 4 The data in the table are from Farid et al4



Reversible P2Y12 …
Chloroquine retinopathy: is there a safe daily dose?
Authors: J.S Marks
Journal: Annals of the Rheumatic Diseases (1982)

Published case reports of chloroquine retinopathy rarely include details of daily dosage, but 30 reports where this information was available included 78 patients who developed impaired visual acuity an 13 had received daily doses of 250 mg or less. Eleven cases of ocular toxicity attributed to chloroquine were reported to the Committee on Safety of Medicines but only 2 developed impaired vision on 250 mg daily. A postal questionnaire among 41 rheumatology and 33 ophthalmology centres showed 2 patients who developed impaired vision as a result of treatment with chloroquine in a daily dose not exceeding 250 mg. Serious visual impairment related to chloroquine rarely occurs if the daily dose does not exceed 250 mg.