tbuckley/cabot-search huggingface dataset:
Abstract 4057: Functional domain of Annexin A4: which domain is indispensable for chemoresistance to platinum drugs.
Authors: Akiko Morimoto, Takayuki Enomoto, Shinya Matsuzaki, Kousuke Hiramatsu, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Takuhei Yokoyama, Satoshi Serada, Tetsuji Naka, Tadashi Kimura
Journal: Cancer Research (2013)

Abstract Background: Platinum drugs are often used for the postoperative adjuvant therapy or treatment in advanced and recurrent ovarian cancer. We have previously reported that ovarian clear cell carcinoma (CCC) has increased expression of Annexin A4 (Anx A4) in comparison with other subtype of ovarian cancer. Enhanced expression of Anx A4 has been shown to induce chemoresistance via extracellular efflux of carboplatin. Purpose: To identify the domain of Anx A4 relevant to chemoresistance. Materials and methods: Anx A4 possesses the NH2-terminal domain and four annexin repeat domains with one Ca2+-binding site in each domain. Deleting annexin repeat domains one by one from C-terminal site, we generated four deletion mutants of Anx A4 named R1, 2, 3, and 4 (arabic figure shows the number of annexin repeat domains). Stable cell lines overexpressing each deletion mutants were established in NUGC3 cells. Chemosensitivity to platinum drugs was evaluated using the MTT assay. Results. Compared with mock transfected cells, all the four deletion mutants induced chemoresistance to both cisplatin and carboplatin. Conclusions. The deletion derivative covering only one annexin repeat domain can induce chemoresistance to platinum drugs. Further study is underway to determine the specific site for chemoresistance of Anx A4. Citation Format: Akiko Morimoto, Takayuki Enomoto, Shinya Matsuzaki, Kousuke Hiramatsu, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Takuhei Yokoyama, Satoshi Serada, Tetsuji Naka, Tadashi Kimura. Functional domain of Annexin A4: which domain is indispensable for chemoresistance to platinum drugs. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4057. doi:10.1158/1538-7445.AM2013-4057
Ventilatory Support by Pacing of the Conditioned Diaphragm in Quadriplegia
Authors: William W. L. Glenn, James F. Hogan, Jacob S. O. Loke, Thomas E. Ciesielski, Mildred L. Phelps, Robin Rowedder
Journal: New England Journal of Medicine (1984)

We provided full-time ventilatory support in five patients with respiratory paralysis accompanying quadriplegia by continuous electrical pacing of both hemidiaphragms simultaneously for 11 to 33 months through the application to the phrenic nerves of a low-frequency stimulus. The strength and endurance of the diaphragm muscle increased with pacing. Biopsy specimens taken from two patients who had uninterrupted stimulation for 6 and 16 weeks showed changes suggestive of the development of fatigue-resistant muscle fibers. When we compared these results with those of our earlier experience with intermittent unilateral stimulation of the diaphragm in 17 patients with respiratory paralysis, we found that continuous bilateral pacing using low-frequency stimulation appeared to be superior because of more efficient ventilation of both lungs, fewer total coulombs required to effect the same ventilation, and absence of myopathic changes in the diaphragm muscle. For patients with respiratory paralysis and intact phrenic nerves, continuous simultaneous pacing of both hemidiaphragms with low-frequency stimulation and a slow respiratory rate is a satisfactory method of providing full-time ventilatory support.
Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction
Authors: Giuseppe Patti, Andrea D'Ambrosio, Simona Mega, Gabriele Giorgi, Enrico Maria Zardi, Domenico Maria Zardi, Giordano Dicuonzo, Aldo Dobrina, Germano Di Sciascio
Journal: Journal of the American College of Cardiology (2004)
Families of patients with premature coronary heart disease: an obvious but neglected target for primary prevention
Authors: C K Chow, A C H Pell, A Walker, C O'Dowd, A F Dominiczak, J P Pell
Journal: BMJ (2007)

Risk of premature coronary heart disease is increased in the families of affected patients. <b>C K Chow and colleagues</b> argue that targeting relatives for primary prevention would be an effective policy
Abstract PR8: From prediction to prognosis and therapeutics: The power of breast cancer transcriptional networks
Authors: Bin Zhang, Jonathan Derry, Eric Schadt, Stephen Friend, Jun Zhu, Xudong Dai, Zhi Wang, Fanyan Meng, Linh Tran, Zhan Zhang, Justin Guinney, Bruce Clurman, Guojun Wu
Journal: Cancer Research (2011)

Abstract Complex human diseases such as cancer are driven by interacting networks at molecular, cellular and environmental levels. Increasingly available large-scale high-throughput genetic and genomic data makes it possible to reconstruct predictive molecular networks that characterize diseases and indentify causal drivers for therapeutic intervention. Here we present an integrative network approach to analyze multiple large scale gene expression datasets in breast cancer. We compiled four large-scale breast cancer gene expression datasets (van't Veer, Dai et al. 2002; Miller, Smeds et al. 2005; Wang, Klijn et al. 2005; Sotiriou, Wirapati et al. 2006). Gene coexpression networks were first constructed on individual datasets to derive gene modules comprised of highly interconnected genes. Gene modules significantly conserved in multiple co-expression networks were then grouped into consensus modules. Meanwhile, Bayesian networks (BN) were also constructed from the individual datasets and combined by union of directed links to form a super BN. The consensus gene modules were used to partition the combined BN into a number of functional regions to derive module based regulatory subnetwork for which key regulators were then identified through key driver analysis. Novel pathways such as ARFs pathways were uncovered to be essential for breast cancer progression and subsequently validated. The predicted novel drivers were systematically validated through a large number of siRNA experiments. The driver genes are not only predictive of survival time and chemotherapy response but also effective in elucidating drug mechanisms. An FDA approved anti-hypertensive drug, predicted by our integrative network analysis to be effective on breast cancer, dramatically and selectively inhibits proliferation of breast cancer cells through inhibition of cell cycle activity while keeping the majority of normal cells alive. Such an integrative network approach and the findings will have significant impact on breast cancer research and drug development, while more broadly facilitating study and treatment of complex human diseases. This abstract is also presented as Poster B21. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR8.
IMWG consensus on maintenance therapy in multiple myeloma
Authors: Heinz Ludwig, Brian G. M. Durie, Philip McCarthy, Antonio Palumbo, Jésus San Miguel, Bart Barlogie, Gareth Morgan, Pieter Sonneveld, Andrew Spencer, Kenneth C. Andersen, Thierry Facon, Keith A. Stewart, Hermann Einsele, Maria-Victoria Mateos, Pierre Wijermans, Anders Waage, Meral Beksac, Paul G. Richardson, Cyrille Hulin, Ruben Niesvizky, Henk Lokhorst, Ola Landgren, P. Leif Bergsagel, Robert Orlowski, Axel Hinke, Michele Cavo, Michel Attal
Journal: Blood (2012)
Preclinical investigation of the pharmacokinetics, metabolism, and protein and red blood cell binding of DRDE-07: a prophylactic agent against sulphur mustard
Authors: Pankaj Verma, Rajagopalan Vijayaraghavan
Journal: Acta Pharmaceutica Sinica B (2014)

DRDE-07, a newly synthesized amifostine analog currently under clinical investigation in a phase I trial, is a potent antidote against sulfur mustard toxicity. The purpose of this research was to evaluate the pharmacokinetic profile of DRDE-07 in female Swiss Albino mice after a single oral dose of 400 or 600 mg/kg. The physicochemical properties of DRDE-07, including solubility, pK a, Log P, plasma protein binding and plasma/blood partitioning, were determined to support the pharmacokinetic characterization. DRDE-07 concentration was determined by an HPLC-UV method. The profile of plasma concentration versus time was analyzed using a non-compartmental model. Plasma protein binding was assessed using ultrafiltration. DRDE-07 appeared rapidly in plasma after oral administration with peak plasma levels (C max) observed in less than 15 min. There was a rapid decline in the plasma levels followed by a smaller second peak about 90 min after dosing. The plasma protein binding of DRDE-07 was found to be less than 25% at all concentrations studied. Plasma clearance of DRDE-07 is expected to be ~1.5 fold higher than the blood clearance of DRDE-07. The probable metabolite of DRDE-07 was identified as phenyl-S-ethyl amine.
Pulmonary Aspiration of Gastric Acid
Authors: Samuel Berkowitz
Journal: JAMA (1962)

<h3>To the Editor:—</h3> In the article "Pulmonary Aspiration of Gastric Acid: Mendelson's Syndrome: Successful Treatment with Lyophilized Urea and Ten Per Cent Invert Sugar" (<i>JAMA</i><b>79</b>:900 [March 17] 1962), there was no direct evidence of aspiration of gastric contents. The more likely explanation of the massive "froth" and pulmonary infiltration was prolonged, partial upper-respiratory obstruction to inspiration. Positive pressure inhalation is not a reliable therapeutic test of the diagnosis of pulmonary edema since it commonly fails to reduce the "amount of froth" unless accompanied by the vaporization of an alcohol or detergent. The administration of lyophilized urea in 10% invert sugar dramatically improved the pulmonary condition at the expense of severe dehydration and a temperature of 108° F. (42.22° C.). The consequent hyperosmolarity of plasma could explain the response of the pulmonary infiltration if it were edema but not the chemical, exudative pneumonitis assumed by the author. His disapprobation
75Se-sodium selenite as a diagnostic aid in the assessment of peripheral pulmonary opacities.
Authors: I D Whitton, A E Houlder
Journal: Thorax (1979)

To establish or exclude the diagnosis of bronchial carcinoma a series of 43 patients with peripheral pulmonary opacities was studied by lung scanning after intravenous injection of 75Se-sodium selenite. A diagnosis was ultimately obtained in all patients. The incidence of both false-positive and false-negative results was high. Selenite was taken up by a range of non-neoplastic processes including inflammatory lesions. The value of the procedure in distinguishing bronchial carcinoma from non-neoplastic conditions of the lung that radiographically mimic carcinoma was not confirmed.
Once-daily Fluticasone Furoate∗ Nasal Spray (FF) Provides 24-hour Relief of the Nasal Symptoms of Seasonal Allergic Rhinitis (SAR) in Children ages 2-11 Years ∗USAN approved name
Authors: E.O. Meltzer, I. Tripathy, J. Lee, J. Lim, A. Ellsworth, E. Philpot
Journal: Journal of Allergy and Clinical Immunology (2007)
Coombs' Positive Reactions Associated With Sodium Cephalothin Therapy
Authors: Harvey R. Gralnick
Journal: JAMA (1967)

Sodium cephalothin (Keflin) has been extensively used in the therapy of gram-negative and gram-positive infections with but few untoward reactions. In a few cases hematological side effects, ie, transient neutropenia—associated in one case with the bone marrow manifestation of maturation arrest, have been reported. Cessation of cephalothin therapy was associated with a prompt recovery from the neutropenia.<sup>1</sup> Our interest in cephalothin began with the case of a 16-year-old boy with anemia and uremia due to congenital absence of one kidney and hypoplasia of the other. He had a positive direct Coombs' (antiglobulin) test without evidence of any blood-cell antibodies in his serum. No antibody could be eluted from his erythrocytes. He was receiving cephalothin intravenously, and the possibility of a serologic abnormality associated with a specific antibody to this drug or cross-reacting anti-peni-cillin antibody was considered. To investigate this possibility, we studied the sera and red blood cells (RBCs)
Abstract 16265: Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9 With a Monoclonal Antibody REGN727/SAR236553, Effectively Reduces Low-Density-Lipoprotein Cholesterol, as Mono or Add-on Therapy in Heterozygous Familial and Non Familial Hypercholesterolemia
Authors: Gary Swergold, William Smith, Scott Mellis, Douglas Logan, Cheryle Webb, Richard Wu, Yunling Du, Therese Krans, Evelyn Gasparino, Evan A Stein
Journal: Circulation (2011)

Since 2003 understanding of proprotein convertase subtilisin/kexin type 9 (PCSK9) has advanced from discovery to in vitro, animal, genetic and observational studies to suggest that inhibition of PC...
Non-restorative surgery in the treatment of Crohn's disease of the large bowel
Authors: J. K. Ritchie, H. E. Lockhart-Mummery
Journal: Gut (1973)

This study gives detailed information on the two principal groups of patients undergoing excisional surgery with a permanent artificial stoma for Crohn9s disease of the large bowel. During the years 1952-71, 64 patients were treated by total proctocolectomy and ileostomy and 26 patients by excision of the distal large bowel and colostomy. In the group of patients undergoing proctocolectomy, there were two postoperative and six late deaths. Of the 56 patients alive at the end of the follow-up period (average length of follow-up 8·1 years), four had shown evidence of recurrent disease. In each case this occurred following a staged proctocolectomy and at, or immediately proximal to, the ileostomy: the shortest interval between surgery and recurrence was just under 10 years. Among the patients treated by excision of the distal large bowel, there were two unrelated late deaths: with an average duration of follow up of 7·3 years, recurrent disease occurred in only one of the 24 patients alive at the concluding date for this study.
Anatomy of the Infant Head
Authors: Jeremiah Kelleher
Journal: JAMA (1987)

Anatomy is for many medical people, this reviewer included, not the most exhilarating and inviting area of study. It was, therefore, with some trepidation that I approached the task of reviewing this atlas of anatomic illustrations, part of The Johns Hopkins Series in Contemporary Medicine and Public Health. Exceeding 450 pages of text and pictures, mainly line drawings, the atlas gives a detailed illustration of the anatomic features of the infant head and neck. Where relevant, comparisons are provided with the fetus and the adult, and when possible, the anatomy is related to functional performance, particularly in relation to the mouth, pharynx, and larynx. Further sections deal with detailed regional anatomy, both skeletal and soft tissue, including the ear, mouth, and upper airways. There is an interesting and most useful appendix on the dimensions of the human larynx during infancy and childhood and 24 tables of measurements. To my great
London professor struck off for bullying and dishonesty
Authors: C. Dyer
Journal: BMJ (1999)

A British professor of respiratory medicine with an international reputation in asthma research was struck off the medical register last week for bullying and threatening junior colleagues and for misleading investigators who were looking into allegations that he had tried to cover up blunders in a clinical drug trial.

The General Medical Council in London found Robert Davies, former professor of respiratory medicine at St Bartholomew's and the Royal London School of Medicine, guilty of serious professional misconduct.

Dr Jeremy Lee-Potter, chairman of the professional conduct committee, told Professor Davies that the committee was “gravely …
Urinary-Tract Infections in Schoolchildren
Authors: Calvin M. Kunin, Norma E. Halmagyi
Journal: New England Journal of Medicine (1962)

THE epidemiologic and clinical features of urinary-tract infections among 13,000 schoolchildren residing in Waynesboro and Charlottesville—Albemarle County, Virginia, have been presented in two previous communications.1 , 2 The present report is concerned with the characterization of the bacteria isolated from the 74 cases detected in these studies. Particular emphasis is placed on the serologic types of Escherichia coli isolated on multiple occasions from the same persons before initiation of specific therapy. Subsequent reports will deal with the immediate and long-term results of therapy, with the nature of the organisms isolated on relapse or reinfection and with measurement of antibody to Esch. coli . . .
China and Population Control
Authors: John R. Dykers
Journal: JAMA (1989)

<h3>To the Editor. —</h3> Dr Ma<sup>1</sup>has written us a beautiful explanation of one child, one family and the application of policy in the Central Kingdom. It is very much a part of the Chinese character that they believe that most social changes originate in the Central Kingdom and gradually flow to the rest of us. (Parisians think everything starts in Paris and Americans think everything begins in California.) In applying the available technology to control population pressures, China certainly has led the way. The principle here is<i>R/(P) × T= Q. R</i>indicates the available resources of the planet;<i>P</i>, the human population; T, the available technology; and Q, the quality of life. China has recognized that to increase the quality of life, the population factor must be controlled because access to resources is limited unless the Chinese wish to engage in aggressive wars to take resources from others.
ULTIMATE RESULTS OF AORTIC TRANSPLANTATIONS
Authors: Alexis Carrel
Journal: The Journal of Experimental Medicine (1912)

In the first experiment, a segment of popliteal artery, extirpated from the leg of a young man and preserved for twenty-four days in cold storage, was transplanted upon the abdominal aorta of a small bitch. The animal lived in excellent health for four years and two months, became pregnant several times, and finally died during labor. The abdominal aorta was normal, but the human arterial segment was slightly dilated, and its wall was composed of connective tissue only. In the second experiment, a segment of dog's jugular vein, preserved for twenty-four hours in cold storage, was transplanted upon the thoracic aorta of a fox terrier. In spite of slight lesions of the cord due to interruption of the aortic circulation during the operation, the animal remained in excellent health. After two years and two months, the dog died of an epidemic disease. The descending aorta was normal. The transplanted segment had about the same caliber as that of the aorta, but its wall was composed of connective tissue, with no evidence of muscular or elastic tissues. In these two experiments, the walls of the transplanted segments contained neither muscle nor elastic tissue fibers and were not thicker than those of the artery. Nevertheless, they were able to withstand the pressure of the blood without undergoing any marked dilatation. If death due to accident had not brought these two experiments to an end, it is probable that the transplanted segment would have successfully resisted the pressure of the blood for a much longer time. As it is, the result shows that, in one experiment after four years and in the other after two years, the segments transplanted upon the abdominal and thoracic aortas were still efficient.
IS THERE MERIT IN THE SO-CALLED "CEREBRAL PALSY" PROGRAM?
Authors: H. R. McCarroll
Journal: JAMA (1949)

To the Editor:—  Spastic paralysis and allied disorders of the central nervous system which must be considered in differential diagnosis have recently been widely publicized under the allinclusive title of cerebral palsy. An attempt is being made to establish expensive and elaborate training programs for the care of these patients in many of our crippled children's clinics. In some instances writers imply that such a program of muscle training and reeducation will afford continuous improvement in muscle control and function and will eliminate need for surgery to correct deformities even in selected cases. What can be expected from a program of this type?  My opinions are based on experience derived from study of a group of 2,096 consecutive cases seen prior to 1948 at the St. Louis Unit of the Shriners' Hospital for Crippled Children. These allied disorders of the central nervous system can be adequately classified under the four
Anti-heat shock protein 70 kDa and 90 kDa antibodies in serum of patients with rheumatoid arthritis
Authors: G Hayem, M De Bandt, E Palazzo, S Roux, B Combe, J F Eliaou, J Sany, M F Kahn, O Meyer
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVES</h3> Stress proteins (HSPs) are highly conserved immunodominant antigens found in various species. The purpose of this study was to assess the prevalence and prognostic significance of antibodies to HSC 70 kDa and HSP 90 kDa in three groups of patients with longstanding rheumatoid arthritis (RA) defined based on the severity of articular erosions. <h3>METHODS</h3> 73 patients with longstanding (&gt; 6 years) RA whose HLA-DR genotype was known were divided in three groups according to Larsen's score and compared with 47 recent onset (&lt;1 year) RA patients and with control groups composed of patients with other inflammatory diseases (n=137) or of normal controls (n=48). IgGs and IgMs to HSC 70 kDa and HSP 90 kDa were determined using an ELISA with purified bovine HSC 70kDa or HSP 90 kDa. <h3>RESULTS</h3> Concentrations of IgGs and IgMs to HSC 70 were significantly increased in 41.1% and 42.5% of longstanding RA patients, respectively. Corresponding figures for IgGs and IgMs to HSP 90 were 39.7% and 56%. IgMs to HSC 70 and HSP 90 were less frequent in recent onset RA (19% and 13% respectively). Among the groups with other inflammatory diseases, only the MCTD group exhibited high frequencies of IgGs to HSC 70 (80%) and HSP 90 (85%). DRB1*0401 positive RA patients (n=23) were not more likely to have increased concentrations of antibodies to HSC 70 kDa or HSP 90 kDa than other RA patients (DR4 positive but DRB1*0401 negative, or DR1 positive, n=31; or negative for both DR4 and DR1, n=14). IgGs to HSP 90 kDa were significantly more frequent (p&lt;0.05) in longstanding RA patients whose Larsen's score was 4 or more (57%) than in those whose Larsen's score was 2 or 3 (39.4%) or less than 2 (16%). No associations were found between Larsen's score and IgGs or IgMs to HSC 70 kDa or IgMs to HSP 90 kDa. A significant correlation was demonstrated between IgGs to HSP 90 kDa and two other serological markers for RA, rheumatoid factor, and anti-Sa antibody; there were no correlations with antikeratin antibody, antiperinuclear factor, or anti-RA 33. <h3>CONCLUSION</h3> IgGs to HSP 90 kDa are most common in longstanding RA patients with articular erosions, suggesting that they may be related to the articular prognosis in RA
Resolution of Chronic Eosinophilic Pneumonia with Corticoid Therapy
Authors: JEAN L. PERRAULT
Journal: Annals of Internal Medicine (1971)

A case of needle biopsy-documented resolution of chronic eosinophilic pneumonia after corticoid therapy is described. The patient presented with nonspecific clinical symptoms, but persistent peripheral blood eosinophilia, migratory pulmonary infiltrates, and pulmonary function impairment suggested the diagnosis; histological proof was secured by means of percutaneous needle biopsy. The patient was then given corticosteroids. Several clinical, radiological, and functional remissions and exacerbations closely followed variations in steroid dosage. A second needle biopsy, done during a period of remission, confirmed the previous assumption by others that steroid therapy leads to resolution rather than organization of the alveolar and interstitial processes of chronic eosinophilic pneumonia.