tbuckley/cabot-search huggingface dataset:
314. Developing Gene Transfer Vectors for Cancer Therapy: Identifying and Overcoming Regulatory Challenges
Authors: Rosemarie Aurigemma
Journal: Molecular Therapy (2006)

A range of regulatory issues must be considered when developing vectors for use in humans. As gene transfer vectors are created and tested according to scientific and technical rationales, the regulatory requirements for use of the vector in humans must also be considered at all stages of development. Some questions that should be addressed when defining an approach to developing vectors for clinical trials are: Is the identity of the vector clearly defined? Are the biological features of the vector and its transgene, when applicable, clearly similar in the animal species used for safety studies and in humans? What levels of vector targeting/tissue specificity or gene expression are necessary? What are the consequences of genetic instability and to what extent must it be measured and/or controlled? Is there a danger of producing an infectious agent that acts horizontally in the population or vertically across generations? Do appropriate assays exist that can answer the aforementioned questions? What are the consequences of long-term presence of the therapeutic agent in the recipient? How will the presence and distribution of the agent be followed in preclinical animal models and in patients? The challenge in answering these and other concerns in vector development lies with the variety of vectors and their chosen targets; each calls for a unique set of requirements, making a "standard" regulatory approach difficult to attain. Some precedence exists for regulatory policies guiding targeted vector development. However, the principles that underlie regulatory policy must be woven into the developmental path for each new agent in order to protect human subjects as well as advance the most scientifically defensible questions through a clinical trial. This presentation will discuss the experiences of the Developmental Therapeutics Program at the National Cancer Institute in partnering with investigators to move therapeutic vectors from bench to bedside. Some basic guidelines will be discussed that can minimize the regulatory hurdles encountered during the development of a variety of targeted vectors for use in humans. This work was funded by and performed at the National Cancer Institute, National Institutes of Health.
Child Abuse and Neglect: A Medical Reference
Authors: Louis Borgenicht
Journal: JAMA (1982)

Continuing self-education by reading current medical literature is occasionally problematic for the practicing physician. Aside from the constraints of time and interest, the dryness of much of the writing in journals and textbooks drives wouldbe readers away. It is exciting, then, to find a comprehensive textbook on a subject of clinical importance and relevance that is not only a true pleasure to read, but also current and highly informative:<i>Child Abuse and Neglect: A Medical Reference</i>. Although the book lists 21 authors, each of its 19 chapters is, with rare exception, of high quality. The four introductory chapters deal with the etiology of child abuse, the physician's role, the law, and prevention. The editor, Norman Ellerstein, uses a device that has been well employed in another modern pediatric text (Klaus and Fanaroff's<i>Care of the High-Risk Neonate)</i>. At the end of his opening chapter he poses "commonly asked medical questions
COMPARISON OF TWO SCINTIGRAPHIC TECHNIQUES IN THE PREOPERATIVE PREDICTION OF REVERSIBLE MYOCARDIAL ASYNERGY
Authors: Alan Rozanski, Daniel S. Berman, Richard Gray, Marge Raymond, Jack M. Gutman, Nancy L. Pantaleo, Jamshid Maddahi, Alan D. Waxman, H. J.C. Swan, J. Matloff
Journal: Clinical Nuclear Medicine (1981)

Rozanski, Alan; Berman, Daniel S.; Gray, Richard; Raymond, Marge; Gutman, Jack M.; Pantaleo, Nancy L.; Maddahi, Jamshid; Waxman, Alan D.; Swan, H. J.C.; Matloff, J. Author Information
Revaccination of High-Risk Adults With Pneumococcal Polysaccharide Vaccine
Authors: Kristin L. Nichol
Journal: JAMA (1999)

1. Flegal KM, Carrol MD, Kuczmarski RJ, Johnson CL. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obes Relat Metab Disord. 1998;22:39-47. 2. Williamson DF, Serdula MK, Anda RF, Levy A, Byers T. Current weight loss attempts in adults: goal, duration, and rate of weight loss. Am J Public Health. 1992; 82:1251-1257. 3. Levy D, Thom TJ. Death rates from coronary disease: progress and a puzzling paradox. N Engl J Med. 1998;339:915-917. 4. Kassirer JP, Angell M. Losing weight: an ill-fated New Year’s resolution. N Engl J Med. 1998;388:52-54. 5. HarrisMI, FlegalKM,CowieCC,et al. Prevalenceofdiabetes, impaired fastingglucose, and impaired glucose tolerance in US adults. Diabetes Care. 1998;21:518-524. 6. Rosamond WD, Chambless LE, Folsom AR, et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med. 1998;339:861-867. 7. Bowen R, Glicklich A, Khan M, et al. Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US Department of Health and Human Services Interim Public Health Recommendations, November 1997. MMWR Morb Mortal Wkly Rep. 1997;46:1061-1066. 8. Meridia [prescribing information]. Mount Olive, NJ: Knoll Pharmaceutical Co; 1998. 9. Sjostrom L, Rissanen A, Andersen T, et al. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998;352:167-172. 10. Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. Diabetes Care. 1998;21:1288-1294. 11. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281:235-242. 12. Little R, Yau L. Intent-to-treat analysis for longitudinal studies with dropouts. Biometrics. 1996;52:1324-1333. 13. Psaty BM, Smith NL, Siscovick DS, et al. Health outcomes associated with antihypertensive therapies used as first-line agents: a systematic review and metaanalysis. JAMA. 1997;277:739-745. 14. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. Study of Health Outcomes of Weight loss (SHOW) Web site. Available at: http://www.ep.niddk.nih.gov/divisions/ddn/SHOW/show.htm. Accessed December 30, 1998. 15. Forster JL, Jeffery RW, Schmid TL, Kramer FM. Preventing weight gain in adults: a pound of prevention. Health Psychol. 1988;7:515-525. 16. Jeffery RW, French SA. Preventing weight gain in adults: design, methods and one year results from the Pound of Prevention study. Int J Obes Relat Metab Disord. 1997;21:457-464.
Abstract 1702: A novel diagnostic approach using genome-wide single nucleotide polymorphism arrays for ovarian metastases in endometrial cancers
Authors: Yuji Ikeda, Katsutoshi Oda, Shunsuke Nakagawa, Satsuki Murayama Hosokawa, Keiko Shoji, Shogo Yamamoto, Shumpei Ishikawa, Yuriko Uehara, Takahiro Koso, Aki Miyasaka, Tomoko Kashiyama, Yutaka Takazawa, Daichi Maeda, Osamu Hiraike Wada, Kei Kawana, Masashi Fukayama, Hiroyuki Aburatani, Tetsu Yano, Shiro Kozuma, Yuji Taketani
Journal: Cancer Research (2012)

Abstract [Introduction] Synchronous cancers involving ovaries as well as uterine corpus are well-known events in gynecologic malignancies. These tumors may be independently derived, non-metastatic tumors (Dual Primary tumors; DP) or a tumor from one organ with metastasis to the other (Single Primary tumor with Metastasis; SPM). In the majority of these synchronous endometrial and ovarian cancers, both tumors are histologically endometrioid adenocarcinomas, which may cause a diagnostic difficulty to distinguish DP and SPM. By genome-wide genotyping, single nucleotide polymorphism (SNP) arrays, we can obtain chromosomal copy number alterations (CNA) throughout the genome in a single assay. We hypothesized that the copy number profiles by SNP arrays might be highly informative for genetic diagnosis in the synchronous endometrioid adenocarcinomas. [Material and Methods] We genetically diagnosed ten tumors from five patients with synchronous endometrial and ovarian carcinomas, using 250K SNP typing arrays and mutational analysis of PIK3CA, PTEN, K-Ras and CTNNB1 (beta-catenin). We evaluated whether conventional pathological diagnosis is compatible with the genetic diagnosis. [Results] Three of the five patients show identical copy number alterations (CNA), including type, loci and degree of each alteration, between the endometrial and the ovarian carcinomas. The other two show CNA only in either endometrial or ovarian carcinoma. All the five tumors possess one or more genetic mutations in the genes examined. One patient showed mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other four showed concordant mutations. Together, four of the five were genetically diagnosed as SPM and the remaining one was as DP. The pathological diagnosis was not in agreement with the molecular diagnosis in four of the five cases. [Conclusion] Our data suggest that most of the copy number alterations might occur before metastases and that genome-wide genotyping may represent a useful approach to distinguish between SPM and DP in synchronous endometrial and ovarian carcinomas. As chromosomal instability is commonly observed in various types of tumors, SNP array genotyping might be applicable to synchronous tumors in other organs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1702. doi:1538-7445.AM2012-1702
MLL-Rearranged Leukemia Is Dependent on Aberrant H3K79 Methylation by DOT1L
Authors: Kathrin M. Bernt, Nan Zhu, Amit U. Sinha, Sridhar Vempati, Joerg Faber, Andrei V. Krivtsov, Zhaohui Feng, Natalie Punt, Amanda Daigle, Lars Bullinger, Roy M. Pollock, Victoria M. Richon, Andrew L. Kung, Scott A. Armstrong
Journal: Cancer Cell (2011)
FRACTURE OF SKULL IN CHILD
Authors: Francis P. Richards
Journal: JAMA (1925)

This case has two chief points of interest: (1) the immediate survival and recovery from an extensive injury to the brain, and (2) its history for the subsequent two or three years. <h3>REPORT OF CASE</h3> In July, 1921, I attended a child just past 4 years of age, who had been found under the front feet of a horse at the head of a dark stall in a barn, where he had been playing. He was carried into the house unconscious. The left side of the head was greatly swollen. The mother tried to revive him by applying cold applications, and friction to the extremities; these measures being without result, he was taken in an automobile over a rough road 40 miles to the nearest town. I saw him about eight hours after he was found. The boy was of slight but wiry build, and deeply comatose. Respiration was slow,
Important Events in Cardiology, 1940-1982
Authors: Howard B. Burchell
Journal: JAMA (1983)

IT SHOULD have been a simple task, in acceding to the invitation of the Editor, to write a short essay entitled "Important Events in Cardiology, 1940-1982: A Retrospective View," but it did not turn out that way. During this, my 50th medical school anniversary, I have pondered how one could choose events that would be unusual milestones in cardiological progress. How could one possibly include so many items deserving of mention? (1)<i>Basic science advances</i>, eg, transmembrane potential recordings in relation to sodium-, potassium-, and calcium-related currents, (2) awe<i>some developments in technology</i>, eg, the new generation of cardiac pacemakers, (3)<i>new methodologies in diagnostic techniques</i>, eg, coronary arteriography, (4)<i>revolutionary approaches to myocardial metabolism evaluation</i>, eg, radionuclide imaging, (5)<i>new drugs</i>for the management of arrhythmias and anginal pain, (6)<i>administrative and societal events</i>such as the establishment of the National Institutes of Health (NIH) (1948), and (7)<i>heart</i>
Medicine Marches On
Authors: Kenneth L. Zucker
Journal: JAMA (1969)

<h3>To the Editor:—</h3> In the Nov 18 issue ofThe Journala statement in the third column of page 1701 reads "Of 25 penicillin-sensitive patients recently treated with cephalothin in five Philadelphia hospitals, one had fatal anaphylactic shock but recovered." Was the patient's name Lazarus?
A comparison of the thrombolytic and hemorrhagic effects of tissue-type plasminogen activator and streptokinase in rabbits.
Authors: G Agnelli, M R Buchanan, F Fernandez, B Boneu, J Van Ryn, J Hirsh, D Collen
Journal: Circulation (1985)

Tissue-type plasminogen activator (t-PA) is a promising thrombolytic agent because it can produce thrombolysis without inducing a plasma proteolytic state. It is uncertain if this potentially important feature renders t-PA less hemorrhagic than other plasminogen activators. We have compared the hemorrhagic and thrombolytic effects of t-PA and streptokinase in rabbits. Streptokinase, 4000 U/kg/hr over 4 hr, failed to produce significant thrombolysis and 8000 U/kg/hr streptokinase over 4 hr produced only 28 +/- 6% thrombolysis. Both streptokinase regimens were associated with a plasmin-mediated plasma proteolytic state and both streptokinase regimens produced a significant increase in hemorrhage that was evident within 15 min of beginning the infusion and was progressive over the 4 hr of drug administration. In contrast, t-PA in a dose of 7500 U/kg/hr produced 35 +/- 6% thrombolysis, but it did not produce a plasmin-mediated plasma proteolytic state or a significant increase in hemorrhage over the 4 hr of infusion. t-PA in a dose of 15,000 U/kg/hr produced 85 +/- 4% thrombolysis but was associated with a plasmin-mediated proteolytic state and produced significant bleeding which, in contrast to streptokinase-induced bleeding, was delayed in onset. Therefore, t-PA induced less hemorrhage than streptokinase at doses that produced more effective thrombolysis. Bleeding with both thrombolytic agents was associated with a plasmin-mediated proteolytic state.
Malignant acanthosis nigricans: potential role of chemotherapy
Authors: None Anderson, None Hudson-Peacock, None Muller
Journal: British Journal of Dermatology (1999)

Journal Article Malignant acanthosis nigricans: potential role of chemotherapy Get access S.H.C. Anderson, S.H.C. Anderson The Kent and Canterbury Hospital, Ethelbert Road, Canterbury, Kent CT1 3NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar M. Hudson‐Peacock, M. Hudson‐Peacock The Kent and Canterbury Hospital, Ethelbert Road, Canterbury, Kent CT1 3NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar A.F. Muller A.F. Muller The Kent and Canterbury Hospital, Ethelbert Road, Canterbury, Kent CT1 3NG, U.K. Muller The Kent and Canterbury Hospital, Ethelbert Road, Canterbury, Kent CT1 3NG, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 141, Issue 4, 1 October 1999, Pages 714–716, https://doi.org/10.1046/j.1365-2133.1999.03116.x Published: 01 October 1999
Utility of the prehospital electrocardiogram in diagnosing acute coronary syndromes: the Myocardial Infarction Triage and Intervention (MITI) project
Authors: Peter J. Kudenchuk, Charles Maynard, Leonard A. Cobb, Mark Wirkus, Jenny S. Martin, J.Ward Kennedy, W.Douglas Weaver
Journal: Journal of the American College of Cardiology (1998)
Antipersonnel landmines: facts, fictions, and priorities
Authors: C. Giannou
Journal: BMJ (1997)

Gerhard Rose, one of Germany's most respected physicians, stood in the prisoner's dock at the Palace of Justice in Nuremberg, Germany, awaiting his sentence for "murders, tortures, and other atrocities committed in the name of medical science."Dr Rose, the department head for tropical medicine of the Robert Koch Institute, was on trial along with 22 of his medical colleagues, for perpetrating "ghastly" and "hideous" experiments on concentration camp prisoners during the war. 1 At one point in the trial when the chief prosecution witness, Dr Andrew C Ivy of the medical school of the University of Illinois, underscored the basic principle "that human experimental subjects must be volunteers," Dr Rose and his defence counsel vigorously objected, arguing that the United States was guilty of similar medical practices and giving several examples to support this contention.
Management of pulmonary artery sling (anomalous left pulmonary artery arising from right pulmonary artery): a conservative approach.
Authors: P D Phelan, A W Venables
Journal: Thorax (1978)

An anomalous left pulmonary artery arising from a right pulmonary artery and passing between the trachea and oesophagus was seen in seven patients over a period of 20 years. All of them had main airway obstruction. Surgical division and re-anastomosis of the anomalous artery in front of the trachea produced an unsatisfactory result in the first two patients. The only surgical procedure undertaken in the subsequent five patients was division of a ligamentum arteriosum; this formed part of a compressing ring in one patient. Three patients, one of whom had associated tracheobronchial stenosis, became completely asymptomatic. Two others, both with tracheobronchial stenosis, still have symptoms; the older has shown considerable improvement, while the younger is only 7 months old. It is suggested that a more conservative approach to the management of this anomaly is justified. In patients with associated tracheobronchial stenosis, symptoms are most probably the result of that anomaly. Surgical division of the anomalous artery is unlikely to be beneficial, and death from postoperative complications frequently occurs. Surgical division of the anomalous artery in patients with extrinsic tracheal compression should be considered only if life is threatened, as spontaneous improvement can be anticipated. Recent advances in respiratory care should assist in the conservative management of distressed infants.
Two paths lead to MS
Authors: Hema Bashyam
Journal: The Journal of Experimental Medicine (2008)

Two T helper (Th) cell subsets trigger the same multiple sclerosis (MS)-like symptoms but varying disease pathologies, say Kroenke et al. (page [1535][1]).

Inflammatory Th1 cells and Th17 cells can both drive experimental autoimmune encephalitis (EAE)—the mouse equivalent of MS. The authors found
PERCUTANEOUS ABSORPTION AND DISTRIBUTION OF 2-NAPHTHOL IN MAN
Authors: H. G. W. M. HEMELS
Journal: British Journal of Dermatology (1972)

Summary.— A procedure is described for determining unchanged and conjugated 2‐naphthol in plasma and urine. The method, based on gas chromatography is rapid and has a limit of detection of approximately 2 g/m/1−1. Twenty‐four hours urine excretion data of 2‐naphthol, after therapeutic application of a 2‐naphthol‐containing ointment on the skin of patients, are reported. Plasma levels of 2‐naphthol and conjugated 2‐naphthol during and after topical treatment with a 2‐naphthol peeling paste were measured in 4 patients. Plasma levels of 2‐naphthol were significantly lower than the plasma levels of conjugated 2‐naphthol. The cutaneous barriers were found to be easily traversed by 2‐naphthol. The relevance of the data for clinical practice is discussed.
" Audi Tertiam Partem."
Authors: Chas. G. Kuhlman
Journal: JAMA (1895)

San Francisco, Cal., July 4, 1895. <h3>To the Editor:</h3> —In the June 29 issue of theJournal, on page 1021, under the head of " A Question of Translation," Dr. G. A. Aschman, of Wheeling, W. Va., takes the liberty to so construe the latter part of my communication of June 15, (appearing under the heading of "<i>Audi Alteram Partem</i>,") as to make it appear that I have been guilty of incorrectly translating the German term " entgiften" which is the opposite of the German term " vergiften"—to poison—and which has no equivalent in the English language—except " disempoison" perhaps. The Doctor, after pretending to be familiar with the expressions of Binz—and after stating that I have no reason to take issue with Binz on his doctrine, sums up his article by stating that it is sometimes dangerous to make a translation when not perfectly familiar with the respective languages.
Some methods of obtaining quantitative structure-activity relationships for quantities of environmental interest.
Authors: M Charton
Journal: Environmental Health Perspectives (1985)

Methods are described for obtaining quantitative structure-activity relationships (QSAR) for the estimation of quantities of environmental interest. Toxicities of alkylamines and of alkyl alkanoates are well correlated by the alkyl bioactivity branching equation (ABB). Narcotic activities of 1,1-disubstituted ethylenes are correlated by the intermolecular forces bioactivity (IMF) equation. When the data set has a limited number of substituents in equivalent positions the group number (GN) equation, derivable from the IMF equation, can be used for correlation. It has been successfully applied to aqueous solubilities, 1-octanol-water partition coefficients, and bioaccumulation factors and ecological magnifications for organochlorine compounds. A combination of the omega method for combining data sets for different organisms with the GN equation has been used to correlate toxicities of organochlorine insecticides in two species of fish. Toxicities of carbamates have been correlated by a combination of the zeta method and the IMFB equation. The ABB and the GN equations are particularly useful in that they generally do not require parameter tables, and that the parameters they use are error-free. The methods presented here, as shown by the examples given, should make it possible to establish a collection of QSAR for toxicities, bioaccumulation factors, aqueous solubilities, partition coefficients, and other properties of sets of compounds of environmental interest.
Reactive Species Mediate Inhibition of Alveolar Type II Sodium Transport during Mycoplasma Infection
Authors: Judy M. Hickman-Davis, Carmel McNicholas-Bevensee, Ian C. Davis, He-Ping Ma, Glenda C. Davis, Charles A. Bosworth, Sadis Matalon
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Mycoplasma pneumoniae is a significant cause of pneumonia in humans.Objectives: To determine the impact of mycoplasma infection and the host inflammatory response on alveolar type II (ATII) cell ion transport in vivo and in vitro.Methods: Mice were infected with M. pulmonis for measurements of alveolar fluid clearance (AFC) in vivo and isolation of ATII cells. ATII cells were infected in vivo for determination of epithelial Na+ channel (ENaC) total and cell surface protein levels by biotinylation and Western blot and in vitro for whole cell patch clamp recording and measurement of nitric oxide (NO) production by chemiluminescence.Results: Mycoplasma infection significantly inhibited AFC at 24 h and total and amiloride-sensitive AFC by 48 h postinfection (pi). In contrast, infected myeloperoxidase-deficient mice had similar basal and amiloride-sensitive AFC values to uninfected control mice at 48 h pi. Addition of forskolin restored total and amiloride-sensitive AFC to control values at 48 h pi. ATII cells isolated from infected mice demonstrated normal α, β, and γ ENaC total protein levels; however, infected whole-lung cell-surface levels of γ ENaC were significantly decreased. Patch-clamp recordings demonstrated a significant decrease in total and amiloride-sensitive Na+ currents at 24 h pi. ATII cells demonstrated a significant increase in the production of NO at 24 h pi and inhibition of NO by ATII cells before infection reversed the decrease in total Na+ currents.Conclusions: These data indicate that mycoplasma infection results in decreased AFC and functional ENaC via the production of reactive oxygen nitrogen intermediates.