tbuckley/cabot-search huggingface dataset:
Roquin Differentiates the Specialized Functions of Duplicated T Cell Costimulatory Receptor Genes Cd28 and Icos
Authors: Michelle A. Linterman, Robert J. Rigby, Raphael Wong, Diego Silva, David Withers, Graham Anderson, Naresh K. Verma, Robert Brink, Andreas Hutloff, Chris C. Goodnow, Carola G. Vinuesa
Journal: Immunity (2009)
Prednisone Therapy for Duchenne's Muscular Dystrophy
Authors: Robert H. Brown
Journal: New England Journal of Medicine (1989)

In the past five years, progress in understanding the molecular basis of Duchenne's muscular dystrophy has been substantial. The affected gene in this disease has been cloned, and its protein product, dystrophin, characterized.1 The importance of dystrophin in the pathogenesis of this disorder has been defined: dystrophin is absent from muscle in Duchenne's muscular dystrophy and is usually present but of abnormal size in Becker's muscular dystrophy, a milder variant.2 Unfortunately, these dramatic advances have not yet had an effect on the clinical management of muscular dystrophy. Duchenne's muscular dystrophy remains invariably fatal. The disease is common, occurring in approximately . . .
Cutting Second-Order Chords Does Not Prevent Acute Ischemic Mitral Regurgitation
Authors: Filiberto Rodriguez, Frank Langer, Katherine B. Harrington, Frederick A. Tibayan, Mary K. Zasio, David Liang, George T. Daughters, Neil B. Ingels, D. Craig Miller
Journal: Circulation (2004)

Cutting anterior mitral leaflet second-order chordae has been proposed for repair in ischemic mitral regurgitation (IMR). We examined the efficacy of such chordal cutting in preventing acute IMR.Six sheep underwent radiopaque marker placement (left ventricle, mitral annulus, papillary muscles [PMs], and leaflets). The largest second-order chord from each PM was encircled with exteriorized wire snares. Three-dimensional marker coordinates were obtained with biplane videofluoroscopy before and during acute ischemia (80 seconds of mid-circumflex occlusion). Color Doppler transesophageal echocardiography was used to grade MR on a 0 to 4+ scale. Data were acquired immediately before and after dividing second-order chordae. Slope of the end-diastolic volume-stroke work relationship (PRSW) was calculated to assess systolic function. Chordal cutting increased anterior leaflet inflection angle (155+/-12 versus 162+/-9 degrees; P=0.03), resulting in a flatter leaflet, but did not increase effective leaflet length (1.97+/-0.24 versus 2.08+/-0.23 cm; P=0.15); PRSW decreased (63+/-15 versus 56+/-12 mm Hg; P=0.008). Both before and after chordal cutting, ischemia caused: Septal-lateral annular dilation (P=0.005), posterior PM displacement away from the mid-septal annulus (P=0.06), increased leaflet tenting area (P=0.001), and increased leaflet tenting volume (P=0.002). Before chordal cutting, MR increased significantly during ischemia (0.5+/-0.3 versus 1.7+/-0.4; P<0.001), and IMR increased similarly even after the second-order chords were cut (0.7+/-0.4 versus 1.9+/-0.9; P<0.001).Cutting second-order chordae resulted in LV systolic dysfunction and neither prevented nor decreased the severity of acute IMR, septal-lateral annular dilation, leaflet tenting area, or leaflet tenting volume.
World Changes: Thomas Kuhn and the Nature of Science
Authors: Richard N. Manning
Journal: JAMA (1994)

<i>World Changes</i>contains papers presented at a 1990 conference, held at the Massachusetts Institute of Technology, devoted to the work of historian and philosopher of science Thomas Kuhn. Among those whose business is thinking about the nature and history of science, Kuhn's 1962 classic<i>The Structure of Scientific Revolutions</i>is beyond question the most widely influential book of this era. <i>Structure</i>was written against the backdrop of the dominant positivistic view that science proceeds by the hyperrational process of strictly deriving observational predictions from candidate theories and then testing them against observations made in experimental settings. In this manner, crucial experiments effectively decide among competing theories, and science gradually converges upon the univocal truths of nature. The positivists themselves were among the first to see the logical and epistemological problems with this simplistic view, but responded by developing probabilistic accounts of confirmation and language-relative accounts of observation to shore it
Initial Analyses of Colon Cancer–Specific Antigen (CCSA)-3 and CCSA-4 as Colorectal Cancer–Associated Serum Markers
Authors: Eddy S. Leman, Robert E. Schoen, Joel L. Weissfeld, Grant W. Cannon, Lori J. Sokoll, Daniel W. Chan, Robert H. Getzenberg
Journal: Cancer Research (2007)

Abstract Colon cancer–specific antigen (CCSA)-3 and CCSA-4 are novel colon cancer markers identified by focused proteomic analysis of nuclear structural proteins. The goal of these studies was to evaluate serum-based CCSA-3 and CCSA-4 in the detection of individuals with preneoplastic and neoplastic lesions using ELISAs. Serum samples from 107 subjects undergoing colonoscopy, 28 subjects with colorectal cancer, and 125 subjects with benign disease or other types of cancer were evaluated. Individuals who underwent colonoscopy were classified into mutually exclusive categories, including normal colon, hyperplastic polyp, nonadvanced adenoma, and advanced adenoma. Sensitivity and specificity for both CCSA-3 and CCSA-4 were evaluated using receiver operating characteristic (ROC) curves. At a cutoff of 2 μg/mL for CCSA-3 and 0.3 μg/mL for CCSA-4, each marker detected all 28 colorectal cancers, for a sensitivity of 100% (lower 95% confidence bound, 89.8%). The sensitivity for detection of the combined end point of colorectal cancer and advanced adenoma for CCSA-3 was 89.1% [95% confidence interval (95% CI), 76.4–96.4%] and for CCSA-4 was 84.8% (95% CI, 71.1–93.7%) and 91.3% (95% CI, 79.2–97.6%) for either marker positive. The specificity in individuals with normal, hyperplastic polyps, or nonadvanced adenomas was 82.0% (95% CI, 72.4–89.4%) and 91.0% (95% CI, 83.0–96.0%) for CCSA-3 and CCSA-4, respectively. ROC curves for CCSA-3 and CCSA-4 reveal an area under the curve of 0.94 (95% CI, 0.90–0.98%). In these initial analyses, CCSA-3 and CCSA-4 show promise as potential serum markers for detection of colorectal cancer and advanced adenomas. [Cancer Res 2007;67(12):5600–5]
Medicare and Drug Pricing
Authors: John K. Iglehart
Journal: New England Journal of Medicine (2003)

In this report, Iglehart describes the debate about Medicare's overpayment to physicians for drugs administered to patients in the outpatient setting, such as chemotherapeutic agents. Oncologists acknowledge that they purchase drugs at prices that are lower than the reimbursement they receive from Medicare, but they argue that they are underpaid for their professional services and practice expenses. Faced with a delicate balancing act, policymakers must weigh the interests of Medicare beneficiaries, physicians, and the public as they work to reform the way in which Medicare pays for drugs.
Comparison of Topoisomerase I Inhibition, DNA Damage, and Cytotoxicity of Camptothecin Derivatives Presently in Clinical Trials
Authors: A. Tanizawa, A. Fujimori, Y. Fujimori, Y. Pommier
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Comparison of Topoisomerase I Inhibition, DNA Damage, and Cytotoxicity of Camptothecin Derivatives Presently in Clinical Trials Get access Akihiko Tanizawa, Akihiko Tanizawa Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. Present Address : A. Tanizawa, Department of Pediatrics, Fuki Medical College, 23 Matsuoka-cho Simoaizuki, Yoshida-gun, Fukui 910-11, Japan. Search for other works by this author on: Oxford Academic PubMed Google Scholar Akira Fujimori, Akira Fujimori Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Yuko Fujimori, Yuko Fujimori Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Yves Pommier Yves Pommier * Laboratory of Molecular Pharmacology, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer InstituteBethesda, Md. *Correspondence to : Y. Pommier, National Institutes of Health, Bldg. 37. Rm. 5C25, Bethesda, MD 20892. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 11, 1 June 1994, Pages 836–842, https://doi.org/10.1093/jnci/86.11.836 Published: 01 June 1994 Article history Received: 13 August 1993 Revision received: 18 February 1994 Accepted: 08 March 1994 Published: 01 June 1994
Erdheim-Chester disease: typical radiological bone features for a rare xanthogranulomatosis
Authors: V Breuil
Journal: Annals of the Rheumatic Diseases (2002)

A 55 year old man was admitted to the rheumatology department owing to inflammatory back pain (occurring at 4 00 am, not aggravated by movement) without sciatica, increasingly severe over two years and associated with asthenia and weight loss (10 kg). No abnormalities were found on physical examination, except for tenderness on palpation of the spinous processes of L5 and S1. There was no significant past medical history. Laboratory tests showed a mild inflammatory picture: erythrocyte sedimentation rate 25 mm/1st h (normal 5–15), C reactive protein 12 mg/l (normal 0–10), fibrinogen 5.1 g/l (normal 2–4). Protein electrophoresis, red and white blood cell count, glucose, renal, and liver function tests were normal. Chemical bone markers (urinary pyridinoline, alkaline phosphatase, osteocalcin, parathormone, 25-hydroxyvitamin D, serum calcium and phosphorus, and urinary calcium and phosphorus) were normal.

Standard lumbar spine and pelvic radiographs were normal.

Technetium-99m bone scintigraphy showed no abnormal uptake in the spine or skull but disclosed an increased peripheral uptake.

A skeletal survey showed multiple mixed bone lesions with sclerotic areas surrounding smaller lytic foci. These roughly bilateral, symmetrical lesions involved the metaphyses and diaphyses of some long bones but spared the epiphyses. Bones affected were the femora, tibiae, radii, wrist, and tarsal bones (fig 1).



 Figure 1  
Skeletal bone radiographs showed bilateral and symmetrical cortical osteosclerosis of the …
Australian university students agree with Clinton's definition of sex
Authors: J. Richters, A. Song
Journal: BMJ (1999)

EDITOR—Since 1988 we have surveyed first year students in behavioural sciences at Macquarie University in Sydney on their attitudes to and knowledge of HIV and AIDS and relevant risk behaviours. In 1998 we asked 545 students aged 17 to 73 (median age 19; 62% under 20) which of the following activities count as “having sex with” someone: tongue kissing, touching or stroking sexual organs with the hand (mutual masturbation), oral sex (mouth on penis or vulva) with or without orgasm, and penetration of the vagina or anus by …
Abstract LB-208: Small interfering RNA library screen to identify therapeutic transcription factor.
Authors: Zhi Hu, Shenda Gu, Joe Gray, Juha Rantala
Journal: Cancer Research (2013)

Abstract Post-genomic analyses of major transcription factor families, in both malignant and non-malignant cell types, have resulted in a broader revision of understanding the biology of transcription factor families. A number of oncogenic transcription factors, such as activator protein (AP)-1, estrogen receptor(ER) and signal transducer and activator of transcription (STAT)-3/STAT-5, are overactivated in human carcinomas. Up to now, three main groups of transcription factors are known to be important in human cancer. Transcription factor-directed anticancer drug development has focused on membrane or cytosolic targeting of molecules acting as ligand receptors. Recent technologies, such as small interfering RNA (siRNA), have shifted transcription factor targeting toward a more sophisticated rationale to elucidate the mechanisms that govern gene expression by analyzing the functions of proteins commonly over-expressed in transformed and malignant cells. In this study, we've applied a cell spot microarray (CSMA) method which provides reproducible multi-parametric phenotypic readouts for large-scale gene knockdown genetic screens. A human transcription factor siRNA library including 350 transcription factor genes which were significantly overexpressed in human breast cancer was screened against 6 breast cancer cell lines including (Triple negative breast cancer, HER2 positive ER positive) SUM149, BT20, HCC1569, SKBR3, MDAMB361 and MCF7 for measuring cell proliferation using EdU incorporation, cell apoptosis with c-PARP staining. We ranked the candidate gene list by the change of the rate of EdU or level of c-PARP or the combination of both. Our data showed that the silencing of LHX1, BCL6, GABPA or SMAD1 increased the c-PARP levels in most of cell lines. The Knockdown of ZNF215, NFATC1, HOXD4 or ZNF169 reduced the levels of EdU staining. Selected siRNAs were then tested on more different breast cancer cell lines to confirm the spectrum of activity. In the near future, based on this pilot screen, a complete siRNA library of transcription factors including 1000 gene list will be tested on our panel of 50 breast cancer cell lines. Our screen will provide comprehensive information on the central role of transcription factor in breast cancer, and will lead to the identity of novel therapeutics selectively against transcription factors. Citation Format: Zhi Hu, Shenda Gu, Joe Gray, Juha Rantala. Small interfering RNA library screen to identify therapeutic transcription factor. [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 LB-208. doi:10.1158/1538-7445.AM2013-LB-208
Selective Inhibition of Inward Rectifier K <sup>+</sup> Channels (Kir2.1 or Kir2.2) Abolishes Protection by Ischemic Preconditioning in Rabbit Ventricular Cardiomyocytes
Authors: Roberto J. Diaz, Carsten Zobel, Hee Cheol Cho, Michelle Batthish, Alina Hinek, Peter H. Backx, Gregory J. Wilson
Journal: Circulation Research (2004)

Volume regulatory Cl- channels are key regulators of ischemic preconditioning (IPC). Because Cl- efflux must be balanced by an efflux of cations to maintain cell membrane electroneutrality during volume regulation, we hypothesize that I(K1) channels may play a role in IPC. We subjected cultured cardiomyocytes to 60-minute simulated ischemia (SI) followed by 60-minute of simulated reperfusion (SR) and assessed percent cell death using trypan blue staining. Ischemic preconditioning (10-minute SI/10-minute SR) significantly (P<0.0001) reduced the percent cell death in nontransfected cardiomyocytes [IPC(CM) 18.0+/-2.1% versus control (C(CM)) 48.3+/-1.0%]. IPC protection was not altered by overexpression of the reporter gene (enhanced green fluorescent protein, EGFP). However, overexpression of dominant-negative Kir2.1 or Kir2.2 genes using adenoviruses (AdEGFPKir2.1DN or AdEGFPKir2.2DN) encoding the reporter gene EGFP prevented IPC protection [both IPC(CM)+AdEGFPKir2.1DN 45.8+/-2.3% (mean+/-SEM) and IPC(CM)+AdEGFPKir2.2DN 47.9+/-1.4% versus IPC(CM); P<0.0001] in cultured cardiomyocytes (n=8 hearts). Transfection of cardiomyocytes with AdEGFPKir2.1DN or AdEGFPKir2.2DN did not affect cell death in control (nonpreconditioned) cardiomyocytes (both C(CM)+ AdEGFPKir2.1DN 45.8+/-0.7% and C(CM)+AdEGFPKir2.2DN 46.2+/-1.3% versus C(CM); not statistically significant). Similar effects were observed in both cultured (n=5 hearts) and freshly isolated (n=4 hearts) ventricular cardiomyocytes after I(K1) blockade with 20 micromol/L BaCl2 plus 1 micromol/L nifedipine (to prevent Ba2+ uptake). Nifedipine alone neither protected against ischemic injury nor blocked IPC protection. Our findings establish that I(K1) channels play an important role in IPC protection.
Action on exercise.
Authors: P Sperryn
Journal: British Journal of Sports Medicine (1991)

The Sports Council's 1978 report on 'The Case for Exercise' made some impact on public thinking in this field.The London Royal College of Physicians' report 'Medical Aspects of Exercise' updates this ground, with only 12 of the 88 references cited in this 11-chapter review dating from before 1980.Basic exercise physiology is reviewed, including effects on young and old; favourable conclusions are drawn about the influence of exercise on different systems or conditions -cardiovascular, respiratory, reproductive, bony, musculoskeletal and the mind, together with diabetes and obesity.Conclusions are clear.Regular aerobic exercise benefits health and much disease; it is best started early and continued for life.Sceptics frown, however, at 'recommendations', including:
Beware the Lean and Hungry Look
Authors: Samuel Vaisrub
Journal: JAMA (1980)

If beauty is in the eye of the beholder, should not the estheticists be eyeing the beholder, exploring his sensibilities, clarifying his preferences, explaining his attitudes? Instead, we find them preoccupied with analysis of the beautiful, be it in nature, people, or art, as if the observer was not there at all, as if beauty inhered in beautiful things independent of time and place, contingent only on its qualities. The narrowness of this approach is attested to by the frequent, almost cyclic changes in the fads of the observer's appreciation of beauty. Take mountains, for instance. Until the romantic poets and painters began to extol their beauty, they were often regarded as nuisances that obstructed the view. In his popular 17th-century travel book<i>Voyage in Italy</i>,<sup>1</sup>Lassels hardly mentions mountain scenery. Or take people. Through the ages until recently, it was the plump rather than the lean who served
Asymptomatic Port-Site Metastasis Following Video-Assisted Thoracoscopic Surgery Detected by FDG-PET/CT
Authors: Guang-Uei Hung, Hon-Ki Hsu, Chia-Hung Kao, Kuang-Yun Chen, Jainn-Shiun Chiu
Journal: Clinical Nuclear Medicine (2010)

We reported a 59-year-old man who had been treated for a rectal adenocarcinoma in May 2005 and also received wedge resection of a solitary metastasis in the left upper lung by video-assisted thoracoscopic surgery (VATS) in September 2008. He underwent FDG-PET/CT scanning in August 2009 due to elevating tumor markers. An FDG-avid lesion was found in the muscles of the left lateral chest wall. Physical examination revealed a palpable nodule just beneath the port-site of VATS. Excisional biopsy confirmed this lesion to be metastatic adenocarcinoma of colorectal origin, considered secondary to tumor cell implantation during previous VATS excision of a metastasis.
Long Hours and Risks to and From Residents
Authors: Howard F. Heller
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Drs Wendt and Yen,<sup>1</sup>in their letter regarding overtired house staff driving home, suggest that residents be provided with sleeping quarters when they are not on call. I doubt that many residents would avail themselves of this service were it available. The attractions of sleeping on one's own firm, queen-sized mattress, with one's own percale sheets on the bed, and with one's pets and/or Significant Other far outweigh the enticement of a bed that, although nearer, would be smaller and less comfortable. In addition, the psychological value of actually getting out of the hospital for a night is incalculable.
Research in the Medical School Curriculum
Authors: Warren H. Gullen
Journal: JAMA (1978)

To  Editor.—  I could not agree more with Robert N. Greenberg regarding  need for medical students to get some education and experience in  scientific method so that they can become better physicians via training  mind to think critically and creatively (239:1162, 1978).  However, I am somewhat concerned about  implications of  types of research experience proposed for  students. For instance, it is suggested that the student might perform a 'record room' research project, making statistical analyses of case histories and symptoms without actually meeting  patients involved. While such studies may be useful educationally if coupled with adequate orientation to research methods and if performed with a critical eye and an awareness of  many limitations of such an approach, it is also possible that bad habits and erroneous concepts can be implanted in  students' minds. After all, record room research and other
Enhanced Cardiomyocyte DNA Synthesis During Myocardial Hypertrophy in Mice Expressing a Modified TSC2 Transgene
Authors: Kishore B. S. Pasumarthi, Hidehiro Nakajima, Hisako O. Nakajima, Shaoliang Jing, Loren J. Field
Journal: Circulation Research (2000)

Abstract —Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the appearance of benign tumors in multiple organs, including the heart. Disease progression is accompanied by homozygous mutation at 1 of 2 loci (designated TSC1 or TSC2), leading to the suggestion that these genes function as tumor suppressors. In this study, we generated a series of TSC2 cDNAs in which one or more structural motifs were deleted, with the hope that expression of the modified gene product would override the growth-inhibitory activity of the endogenous TSC2 gene product. Several of the modified cDNAs enhanced growth rate, increased endocytosis, and promoted aberrant protein trafficking when expressed in NIH-3T3 cells, thereby mimicking phenotypes typical of TSC2-deficient cells. Surprisingly, targeted expression of the most potent TSC2 cDNA to the heart did not perturb cardiac development. However, the level of cardiomyocyte DNA synthesis in adult transgenic mice was elevated &gt;35-fold during isoproterenol-induced hypertrophy compared with their nontransgenic siblings. These results suggest that alteration of TSC2 gene activity in combination with β-adrenergic stimulation can reactivate the cell cycle in a limited number of terminally differentiated adult cardiomyocytes.