tbuckley/cabot-search huggingface dataset:
A Phase I Study of Telomerase-specific Replication Competent Oncolytic Adenovirus (Telomelysin) for Various Solid Tumors
Authors: John Nemunaitis, Alex W Tong, Michael Nemunaitis, Neil Senzer, Anagha P Phadke, Cynthia Bedell, Ned Adams, Yu-An Zhang, Phillip B Maples, Salina Chen, Beena Pappen, James Burke, Daiju Ichimaru, Yasuo Urata, Toshiyoshi Fujiwara
Journal: Molecular Therapy (2009)

A phase I clinical trial was conducted to determine the clinical safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. A single intratumoral injection (IT) of Telomelysin was administered to three cohorts of patients (1 x 10(10), 1 x 10(11), 1 x 10(12) viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen patients with a variety of solid tumors were enrolled. IT of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). hTERT expression was demonstrated at biopsy in 9 of 12 patients. Viral DNA was transiently detected in plasma in 13 of 16 patients. Viral DNA was detectable in four patients in plasma or sputum at day 7 and 14 post-treatment despite below detectable levels at 24 h, suggesting viral replication. One patient had a partial response of the injected malignant lesion. Seven patients fulfilled Response Evaluation Criteria in Solid Tumors (RECIST) definition for stable disease at day 56 after treatment. Telomelysin was well tolerated. Evidence of antitumor activity was suggested.
Intravascular ultrasound imaging in acute aortic dissection
Authors: Andrew R. Weintraub, Raimund Erbel, Günter Görge, Steven L. Schwartz, Junbo Ge, Thomas Gerber, Jürgen Meyer, Tsui-Lieh Hsu, Robert Bojar, Sabino Iliceto, L. Carella, Paolo Rizzon, Isidre Vilacosta, Javier Goicolea, Jose Zamorano, Fernando Alfonso, Natesa G. Pandian
Journal: Journal of the American College of Cardiology (1994)
Abnormal Hemodynamic Function After Disc Mitral Valve Replacement
Authors: JOHN H. K. VOGEL, BRUCE C. PATON, HUGH R. OVERY, S. GILBERT BLOUNT
Journal: Circulation (1969)

Although disc valves have been used extensively for mitral valve replacement, few long-term hemodynamic studies are available. Twenty-five patients received a Kay-Shiley valve, and hemodynamic studies were obtained in 17 patients at an average interval of 15 months after operation. Left ventricular cineangiograms revealed mitral insufficiency in 8 of 15 patients. In three patients a poorly contracting myocardium was associated with elevated left ventricular end-diastolic pressures, suggesting the possibility of acquired endocardial fibroelastosis. The embolic rate was 38%. Two valves became severely stenosed, and two had severe paravalvular leaks which required replacement. Although most patients were improved symptomatically and hemodynamic studies revealed improvement, all had abnormal valve function, particularly during exercise.
Canada's bill tries to beat fraud
Authors: D. Spurgeon
Journal: BMJ (1996)

The Ontario government has paid a general practitioner's Medicare bill for a heart-lung transplant operation that the practitioner claimed to have carried out in a patient's home under local anaesthesia. Dr Mike Dunn of Georgetown said that he submitted the bill to test the system. The “operation” cost the government nearly $C1793 (pounds sterling900), but Dr Dunn has said he will not keep the money. “When they can pass …
Cross-presentation by dendritic cells from live cells induces protective immune responses in vivo
Authors: Diana Matheoud, Leila Perié, Guillaume Hoeffel, Lene Vimeux, Isabelle Parent, Concepción Marañón, Pierre Bourdoncle, Laurent Renia, Armelle Prevost-Blondel, Bruno Lucas, Vincent Feuillet, Anne Hosmalin
Journal: Blood (2010)
Effect of D(-)penicillamine on chronic experimental arthritis in rabbits.
Authors: I M Hunneyball, G A Stewart, D R Stanworth
Journal: Annals of the Rheumatic Diseases (1977)

Preliminary observations on the effect of D(-)penicillamine on chronic antigen-induced experimental arthritis in rabbits are reported. Daily oral administration of penicillamine, at a dose equivalent to that usually administered to rheumatoid arthritis patients, diminished the arthritis in 2 out of 3 animals as assessed by both measurement of joint circumference and histological examination.
Abstract 1969: Mapping the cross talk between parathyroid hormone related protein (PTHrP) and Integrins α6 and β4 in prostate cancer cells
Authors: Vandanajay Bhatia, Ramanjaneya V. Mula, Miriam A. Falzon
Journal: Cancer Research (2011)

Abstract Prostate carcinoma is a leading cause of cancer deaths in men in the United States. An estimated 217,730 new cases and 32,050 deaths from prostate cancer have been reported in 2010 by the National Cancer Institute. For a cancer cell to become malignant it must adopt mechanisms to escape and survive outside its original environment, thus avoiding apoptosis. Parathyroid hormone-related protein (PTHrP) is among the many factors that contribute to this pro-survival state. The mechanisms through which PTHrP affects cell malignancy are not well understood. Our previous studies have shown that PTHrP increases cell-surface levels of integrin α6β4 in prostate cancer cells. Over-expression of integrin α6β4 correlates with increased tumor invasion and metastasis. Integrin α6β4 also acts as a signaling molecule that activates anti-apoptotic phosphoinositide 3-kinase (PI3K) signaling pathways. The mechanism through which PTHrP increases α6 and β4 integrins levels is not clear. We report that in PTHrP over-expressing prostate cancer cell lines (C4-2 and PC-3), the activity of α6 and β4 promoters is increased by ∼ 2.5 fold. We have also found increased NF-κB promoter activity in C4-2 and PC-3 cell lines as a result of PTHrP over-expression. Identification of elements within the integrin α6 and β4 gene promoters that are regulated by PTHrP signaling can provide valuable information regarding the mechanism of the PTHrP action in cancer cell survival and invasion. PTHrP also regulates α6 and β4 protein levels via a post-translational pathway, since the PTHrP protein half-life is higher in PTHrP-over expressing cells in comparison to empty vector control cells. This effect is mediated via the proteasome pathway, as ubiquitinated α6 and β4 levels are reduced in PTHrP over-expressing cells. Our future goals are to map the regulatory elements like NF-κB in the α6 and β4 integrin promoters that are regulated by PTHrP, and to identify the pathways via which PTHrP regulates the proteasome pathway. This might help understand the mechanism through which PTHrP acts in prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1969. doi:10.1158/1538-7445.AM2011-1969
Psychopathology and Mental Retardation
Authors: IRVING PHILIPS
Journal: American Journal of Psychiatry (1967)

A study of 227 retarded children and their families revealed that emotional maladjustment more often than not accompanies retardation. The author points out, however, that disturbed behavior in the retarded is not due primarily to limited intellectual capacities but to delayed, disordered personality functions and disturbed interpersonal relationships with meaningful people in the environment.
"INTERNIST" OR "INTERNALIST"
Authors: H. A. Royster
Journal: JAMA (1927)

To the Editor:  —At the suggestion of a philologic nonmedical relative, I propose seriously dropping the term internist and using internalist in its stead.  worthy practitioner of internal medicine should not have a single syllable lopped from his title, nor should he be designated by a name so nearly allied to the word intern. In the sense herein expressed internalist was used first by me in an address, The Surgeon's Heritage and Outlook, read before the Alabama Medical Association, April 22, 1925, and published in theMedical Journal and Record, Oct. 7, 1925.
EARLY DIAGNOSIS AND PROPER MANAGEMENT IN CERVICAL CANCER
Authors: DANIEL G. MORTON
Journal: JAMA (1942)

The most definite fact known regarding cancer is that with modern methods of treatment a reasonable hope of cure is absolutely dependent on an early diagnosis. It is a source of great satisfaction that many thousands of men and women are living in the United States today who were treated for cancer more than five years ago. On the other side of the ledger is the depressing realization that these thousands represent scarcely one fourth of the total number treated. The explanation for this relatively small salvage lies principally in the fact that the majority of persons seek treatment only after the disease is well advanced. There can be no doubt of this explanation, for there is ample proof of the relative hopelessness of the disease when it is advanced and the good results obtainable when it is early, in the published reports of the world. By way of illustration,
Calmodulin and Ca<sup>2+</sup>/calmodulin kinases in the heart – Physiology and pathophysiology
Authors: Lars S. Maier, Donald M. Bers, Joan Heller Brown
Journal: Cardiovascular Research (2007)

this issue.Original articles in the series are by Yurukova et al. [10] (pages 678-688) and (pages 689-698), also in this issue.Over the last decade our view of calmodulin and Ca 2+ / calmodulin kinase (CaMK) in the heart has progressed extensively.This includes improved understanding of the fundamental CaMKII structure, function, and physiological roles [1,2], and more specifically how CaMKII functions in cardiac excitation-contraction coupling [3] and pathophysiological conditions such as hypertrophy and heart failure [4].Previous reviews on these topics, including the latter in Cardiovascular Research in 2004 that could be said to initiate the present series, have set the backdrop for the broader series of reviews on the burgeoning CaMKII field in the heart in this Review Focus issue.What drives the current interest in calmodulin and CaMK in the heart?One factor is the potential for calmodulin and CaMK to be intrinsically dependent on changes in intracellular Ca 2+ concentration [Ca 2+ ], which regulates not only cardiac contractility but also serves as a ubiquitous second messenger.Indeed, due to the frequent changes in [Ca 2+ ] during systole and diastole, the activity of calmodulin and CaMK can be regulated on a beat-to-beat basis, can exhibit memory (or signal integration), and can participate in both very local and distant signaling within the cell.Thus, during short-term processes
Renal Cortical Retention of Tc-99m MAG3 in Hypotension
Authors: SCOTT A. RABER, FRANK V. SCHRAML, EUGENE D. SILVERMAN
Journal: Clinical Nuclear Medicine (1997)

A three-year-old boy with a history of resected posterior urethral valves had persistent bilateral megaureter and ureterohydronephrosis. Renal scintigraphy was performed within 1 hour of cystoscopy. The initial scintigrams showed prompt cortical uptake of Tc-99m MAG3 with persistence of cortical activity both before and after the administration of furosemide. The patient's cystoscopy had been conducted under heavy general anesthesia and episodic hypotension accompanied the anesthesia. The patient was found to be significantly dehydrated during the initial diuretic renogram. The persistence of cortical activity, similar to the postcaptopril effect in renovascular hypertension, reflects the hypotension that resolved on follow-up evaluation with adequate hydration. Hypotension should be added to the differential diagnosis of persistent cortical activity.
TUBERCULOSIS OF THE TRACHEA AND BRONCHUS
Authors: MERVIN C. MYERSON
Journal: JAMA (1941)

Tuberculosis of the trachea and bronchus is the most discussed phase of diseases of the chest today. Numerous studies have appeared in recent years which have served to stimulate interest and encourage further effort. This condition had been recorded by pathologists long before the subject claimed the attention of the clinician. Carswell1and Louis2reported their autopsy results as long ago as 1838 and 1844 respectively. Prior to 1932 an occasional unanticipated bronchoscopic observation was reported. Since then bronchoscopy has been frequently performed on tuberculous patients. The writings of Krause,3Schonwald,4Andrews,5Vinson,6Eloesser,7Van Allen,8McConkey and Greenberg,9Samson,10Barnwell,11Bugher, Littig and Culp,12Ornstein and Epstein,13Werner,14Kernan,15Ballon,16Phelps17and others have contributed a share toward a better understanding of this subject.  This paper is based on clinical observations and
Abstract 4413: STX140 is an orally bioavailable microtubule targeting agent with no associated peripheral neuropathy and potent anti-metastasis efficacy in vivo
Authors: Simon P. Newman, Paul A. Foster, Joanna M. Day, Mathew P. Leese, Barry VL Potter, Michael J. Reed, Atul Purohit
Journal: Cancer Research (2010)

Abstract There is a continued need for orally bioavailable anti-cancer compounds that exhibit good efficacy and with a more favourable toxicity profile than current ‘traditional’ cytotoxics. The microtubule disruptor, STX140 has previously been shown to have excellent oral bioavailability and significantly reduce tumor growth in vivo. These data presented here show STX140 to: lack significant neuropathy in a validated in vivo behavioural model and to significantly reduce metastasis in a highly aggressive orthotopic model of breast cancer. To assess the potential for neurotoxicity animals were dosed with, vehicle (0.5% methlycellulose), STX140 (20 mg/kg p.o. 5/7 × 4) or Taxol (15 mg/kg i.v weekly x 4). Thermal hyperalgesia, as assessed by paw withdrawal latency, was measured every 3-4 days using Hargreaves Plantar equipment. The 4T1 murine tumor cell line was used to establish orthotopic tumors in the mammary fad pads of nude mice. After 28 days dosing, as above, tumor size, number of lung and liver metastasises were recorded. Additionally relative levels of circulating tumor cells (CTCs) were assessed by quantifying the number of viable tumor cell colonies grown from 30 µL of blood taken by cardiac puncture at day 28. In the thermal hyperalgesia model of neuropathy Taxol caused a significant decrease in paw withdrawal latency from day 14 till the end of study, in contrast there were no significant changes in withdrawal times in either the vehicle or STX140 dosed groups. In the 4T1 xenograft study both Taxol and STX140 reduced, tumor volume, extent of lung metastasis and number of viable CTCs in the blood relative to vehicle. In a separate study STX140 but not Taxol caused a significant improvement in survival. These studies highlight the excellent efficacy of the orally bioavailable anti-cancer agent STX140 in a highly aggressive model of breast cancer. STX140 may offer a major additional advantage over existing drugs as the most common dose limiting toxicity of neuropathy, is negated / minimised. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4413.
How can quality of health care be safeguarded across the European Union?
Authors: Helena Legido-Quigley, Martin McKee, Kieran Walshe, Rosa Suñol, Ellen Nolte, Niek Klazinga
Journal: BMJ (2008)

Can Europeans be confident about the quality of care received in another EU country? Helena Legido-Quigley and colleagues discuss the various mechanisms at work across Europe to ensure quality and safety
Predominance of histocompatibility antigen HL-A8 in patients with gluten-sensitive enteropathy
Authors: Z. Myron Falchuk, G. Nicholas Rogentine, Warren Strober
Journal: Journal of Clinical Investigation (1972)

HL-A phenotypes were determined in 24 unrelated patients with gluten-sensitive enteropathy (GSE) using a lymphocyte microcytotoxicity test. 21 of the 24 patients had HL-A8 in the second segregant series, a frequency of 0.875. In contrast, the HL-A8 frequency in 200 normal individuals was 0.215 (difference significant at P < 0.002), and in 6 patients with villous atrophy due to tropical sprue or hypogammaglobulinemia the HL-A8 frequency was 0.17 (difference from normal not significant). The HL-A types in the families of three HL-A8 positive patients with GSE indicated that the HL-A8 antigen was inherited as an autosomal dominant. Frequencies of the other HL-A antigens in the GSE group did not differ significantly from that of the normal group. These findings are compatible with the hypothesis that GSE is due to the presence of an abnormal "immune response (Ir) gene," leading to the production of pathogenic antigluten antibody or, alternatively, to the presence of a particular membrane configuration leading to the binding of gluten to epithelial cells with subsequent tissue damage.
Excessive hepatomegaly of mice with hepatocyte-targeted elimination of integrin linked kinase following treatment with 1,4-bis [2-(3,5-dichaloropyridyloxy)] benzene
Authors: Shashikiran Donthamsetty, Vishakha S. Bhave, Corrine S. Kliment, William C. Bowen, Wendy M. Mars, Aaron W. Bell, Rachel E. Stewart, Anne Orr, Chuanyue Wu, George K. Michalopoulos
Journal: Hepatology (2010)

TCBOPOP (1,4-bis [2-(3,5-dichaloropyridyloxy)] benzene) an agonist of the constitutive androstane receptor (CAR), produces rapid hepatocyte hyperplasia and hepatomegaly in the absence of hepatic injury. In this study we demonstrate that integrin-linked kinase (ILK), which is involved in transmission of the extracellular matrix (ECM) signaling by way of integrin receptors, plays an important role in regulating TCPOBOP-induced proliferation of hepatocytes and hepatomegaly. Hepatocyte-specific ILK knockout mice (ILK/liver-/- mice) and wildtype mice (WT) were given a single dose of TCPOBOP (3 mg/kg) by oral gavage. Mice were sacrificed at days 1, 2, 5, and 7 after TCPOBOP administration. WT mice showed maximum proliferation on days 1 and 2, which came back to baseline levels by days 5 and 7 after TCPOBOP administration. The ILK/liver-/- mice, on the other hand, showed a prolonged and a sustained proliferative response as evident by an increased number of proliferative cell nuclear antigen assay (PCNA)-positive cells even at days 5 and 7 after TCPOBOP administration. At day 7 the WT mice showed close to a 2.5-fold increase in liver weight, whereas the ILK/liver-/- mice showed a 3.7-fold increase in liver weight. The prolonged proliferative response in the ILK/liver-/- mice seems to be due to sustained induction of CAR leading to sustained induction of c-Myc, which is known to be a key mediator of TCPOPOP-CAR induced direct liver hyperplasia.The data indicate that ECM-mediated signaling by way of ILK is essential for adjustment of final liver size and proper termination of TCPOBOP-induced proliferation of hepatocytes.
Abstract 1208: Elucidating possible functional implications of osteosarcoma risk-associated genetic level alterations in IGF2R
Authors: Sajida Piperdi, Yu Cao, Richard Gorlick
Journal: Cancer Research (2011)

Abstract To address the need for novel osteosarcoma (OS) treatment regimens with greater efficacy and less toxicity, attention has been focused on developing antibodies that target components of the insulin-like growth factor (IGF) pathway, particularly insulin-like growth factor 1 receptor tyrosine kinase (IGF1R). IGF1R and its two ligands, insulin-like growth factor 1 (IGF1) and insulin-like growth factor 2 (IGF2), are known to be over-expressed in several cancers including OS and have roles in regulating cellular growth and proliferation. Clinical trials of IGF1R-inhibiting antibody therapies in OS, however, have returned mixed results. Studies aimed at elucidating the biologic basis of this differential clinical sensitivity to IGF1R-targeting therapeutic agents are currently underway. Interestingly, recent studies from our lab show that IGF2R is consistently over-expressed, relative to other known transmembrane receptors, on the cell surface, across 4 standard and 10 patient-derived OS cell lines. Coupled with results from concurrent experiments suggesting a lack of IGF1R copy number amplification in the majority of tested patient-derived OS samples and xenograft models, we chose to focus our next set of studies on IGF2R_aiming to characterize significant genetic variations within this gene and any functional implications, thereby elucidating the link, if any, between IGF2R's mutational status and its cell surface expression in OS. Relative quantification studies, done via real-time PCR, demonstrated variable IGF2R gene expression across 27 patient-derived OS samples, 4 xenograft models, and 4 standard cell culture (serum-starved) lines. Using the CaCo-2 cell line as the calibrator, 12 out of 27 patient-derived OS samples showed increased IGF2R gene expression, while none of the xenograft models or the standard OS cell lines did. Ongoing studies will examine the relationship between genetic level alterations in IGF2R and its patterns of expression; common IGF2R SNPs will be genotyped, first in the four available OS xenograft models. Findings will be correlated with known patterns of clinical response/sensitivity to IGF1R-targeted therapy tested on these models. The same SNPs will then be genotyped in the patient-derived OS samples and standard cell culture lines. Depending on the results obtained from these initial studies, further experiments can be designed to sequence/genotype other suspect coding regions on the IGF2R gene that may contain functionally significant mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1208. doi:10.1158/1538-7445.AM2011-1208
Testing for the Integrity of Blinding in Clinical Trials: How Valid Are Forced Choice Paradigms?
Authors: Louise Sharpe, Bridget Ryan, Simon Allard, Tom Sensky
Journal: Psychotherapy and Psychosomatics (2003)

&lt;i&gt;Background:&lt;/i&gt; In randomised controlled trials, an increasingly used test of the ‘blindness’ of assessors is to have them guess the group to which each participant has been allocated. Because assessors are usually aware of the trial hypotheses, we predicted that trial participants who showed the greatest improvement would be assumed by an assessor to have been in the ‘preferred intervention’ group. &lt;i&gt;Methods:&lt;/i&gt; Data were derived from a trial in recent-onset rheumatoid arthritis comparing cognitive behavioural therapy plus routine care with routine care alone. &lt;i&gt;Results:&lt;/i&gt; Although in this trial assessor blindness was demonstrated, patients ‘guessed’ by the assessor to be in the cognitive therapy group showed significantly greater improvements than those predicted to have received routine care alone in variables predicted to change in the study protocol. &lt;i&gt;Conclusions:&lt;/i&gt; These results indicate that even if an assessor’s guesses about patient group allocations are more accurate than expected by chance, this would not necessarily demonstrate failure of blinding. This casts further doubt on the validity of forced choice paradigms in testing the integrity of blinding in clinical trials.