tbuckley/cabot-search huggingface dataset:
Genetic Vaccines for Anthrax Based on Recombinant Adeno-associated Virus Vectors
Authors: Te-Hui Liu, Jon Oscherwitz, Bruce Schnepp, Jana Jacobs, Fen Yu, Kemp B Cease, Philip R Johnson
Journal: Molecular Therapy (2008)

Bacillus anthracis represents a formidable bioterrorism and biowarfare threat for which new vaccines are needed with improved safety and efficacy over current options. Toward this end, we created recombinant adeno-associated virus type 1 (rAAV1) vectors containing synthetic genes derived from the protective antigen (PA) or lethal factor (LF) of anthrax lethal toxin (LeTx) and tested them for immunogenicity and induction of toxin-neutralizing antibodies in rabbits. Codon-optimized segments encoding activated PA (PA63), or LF, were synthesized and cloned into optimized rAAV1 vectors containing a human cytomegalovirus (hCMV) promoter and synthetic optimized leader. Serum from rabbits immunized intramuscularly with rAAV1/PA (monovalent), rAAV1/LF (monovalent), rAAV1/PA + rAAV1/LF (bivalent), or rAAV1/enhanced green fluorescent protein (control) exhibited substantial PA- and LF-specific antibody responses at 4 weeks by both western blot (> 1:10,000 dilution) and enzyme-linked immunosorbent assay (ELISA) (mean end-point titer: 32,000-260,000), and contained anthrax LeTx-neutralizing activity in vitro, with peak titers approximating those of a rabbit hyperimmune antisera raised against soluble PA and LF. Compared to the monovalent groups (rAAV1/PA or rAAV1/LF), the bivalent group (rAAV1/PA + rAAV1/LF) exhibited marginally higher ELISA and neutralization activity with dual specificity for both PA and LF. The finding of robust neutralizing antibody responses after a single injection of these rAAV1-based vectors supports their further development as candidate anthrax vaccines.
Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet
Authors: Wei Ling Lau, Elizabeth M. Leaf, Ming Chang Hu, Marc M. Takeno, Makoto Kuro-o, Orson W. Moe, Cecilia M. Giachelli
Journal: Kidney International (2012)
<i>SYT–SSX</i>Gene Fusion as a Determinant of Morphology and Prognosis in Synovial Sarcoma
Authors: Akira Kawai, James Woodruff, John H. Healey, Murray F. Brennan, Cristina R. Antonescu, Marc Ladanyi
Journal: New England Journal of Medicine (1998)

Synovial sarcomas account for up to 10 percent of soft-tissue sarcomas and include two major histologic subtypes, biphasic and monophasic, defined respectively by the presence and absence of glandular epithelial differentiation in a background of spindle tumor cells. A characteristic SYT–SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas. The translocation fuses the SYT gene from chromosome 18 to either of two highly homologous genes at Xp11, SSX1 or SSX2. SYT–SSX1 and SYT–SSX2 are thought to function as aberrant transcriptional regulators. We attempted to determine the influence of the two alternative forms of the SYT–SSX fusion gene on tumor morphology and clinical outcome in patients with this sarcoma.
The FDA Follies
Authors: Leo E. Hollister
Journal: JAMA (1995)

Being commissioner of the Food and Drug Administration (FDA) must be one of the worst jobs possible. A new commissioner enters with great zeal, but he must respond to all manner of political pressures. A vast bureaucracy of civil servants, the majority of whom have been with the agency longer than any commissioner (in one year during the 1960s, the FDA had three), is not much moved by a new face at the top. Areas of responsibility are ever increasing, including medical devices and the products of the biotechnology explosion, but the number of employees does not increase commensurately. As Herbert Burkholz has put it, in a somewhat scathing review of the agency as it existed during the 1980s, [t]he FDA was, then as now, a federal agency subject in the main to the wishes and even the whims of the party in power. It could propose, advocate, argue and
Functional significance of hypertrophy of the noninfarcted myocardium after myocardial infarction in humans.
Authors: L E Ginzton, R Conant, D M Rodrigues, M M Laks
Journal: Circulation (1989)

Hypertrophy of the noninfarcted left ventricle as a chronic response to myocardial infarction has been demonstrated in animals and at autopsy in humans. However, the functional significance of postmyocardial infarction hypertrophy is a subject of dispute. The purpose of this study was to determine the time course of development of postmyocardial infarction hypertrophy of the noninfarcted myocardium in humans and to assess its functional significance. Subcostal view, two-dimensional echocardiograms were recorded at rest and during peak exercise, 6 and 40 weeks postmyocardial infarction in 45 patients (16 anterior, 20 inferior, nine non-Q wave infarcts), for measurement of left ventricular mass and ejection fraction. The left ventricular mass index increased from 94 +/- 30 to 118 +/- 27 g/m2 (p less than 0.01) during the time of the two studies. There was a significant correlation between the change in left ventricular mass index and improved resting ejection fraction (r = 0.48, p less than 0.001) and exercise ejection fraction (r = 0.48, p less than 0.001) at the follow-up study. Of the 32 patients who increased their left ventricular mass index greater than 7%, 18 improved their rest ejection fraction greater than 0.05 units and 17 improved their exercise ejection fraction greater than 0.05 units. Conversely, of the 13 patients who failed to increase their left ventricular mass index, only three improved their rest ejection fraction and one improved the exercise ejection fraction (Fisher's exact test, p less than 0.05). We reached three conclusions. First, in humans, significant hypertrophy of the noninfarcted myocardium can be detected by two-dimensional echocardiography, 9 months postmyocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
Determinants of Increased Regional Left Atrial Coagulation Activity in Patients With Mitral Stenosis
Authors: Roger E. Peverill, Richard W. Harper, John Gelman, T. Eng Gan, Geoff Harris, Joseph J. Smolich
Journal: Circulation (1996)

Recent evidence suggests that regional left atrial coagulation activity may be increased in mitral stenosis and perhaps contribute to the pathophysiology of left atrial thrombus. However, the relation of left atrial coagulation activity to factors that predispose to left atrial thrombus formation is unknown, and the relation between left atrial and systemic coagulation activities is unresolved.Left atrial and peripheral venous levels of the coagulation marker prothrombin fragment 1 + 2 (F1 + 2) were measured in 32 patients with mitral stenosis with normal clotting times and no left atrial thrombus who were undergoing percutaneous balloon mitral valvuloplasty. Baseline peripheral venous F1 + 2 levels, measured at the beginning of the valvuloplasty procedure, did not differ from those of 30 age-matched control patients. Prevalvuloplasty left atrial F1 + 2 levels, obtained immediately after transseptal puncture, were similar to femoral venous levels in patients without left atrial spontaneous echo contrast (LASEC) (0.81 +/- 0.32 versus 0.81 +/- 0.27 nmol/L, n = 7) but greater than femoral venous levels in patients with LASEC and either sinus rhythm (1.57 +/- 0.86 versus 0.99 +/- 0.38 nmol/L, n = 16, P < .001) or atrial fibrillation (1.52 +/- 0.69 versus 0.85 +/- 0.33 nmol/L, n = 9, P < .003). Furthermore, LASEC emerged as the only significant predictor of increased regional left atrial coagulation activity (P = .005) on stepwise multivariate logistic regression analysis.Increased regional left atrial coagulation activity in mitral stenosis occurs in the presence of LASEC, is evident in either sinus rhythm or atrial fibrillation, and is associated with normal systemic coagulation activity.
Clinical usefulness of novel prognostic biomarkers in patients on hemodialysis
Authors: Alberto Ortiz, Ziad A. Massy, Danilo Fliser, Bengt Lindholm, Andrzej Wiecek, Alberto Martínez-Castelao, Adrian Covic, David Goldsmith, Gültekin Süleymanlar, Gérard M. London, Carmine Zoccali
Journal: Nature Reviews Nephrology (2011)
Lymphocytic Choriomeningitis Virus in Man
Authors: Rudolf Deibel
Journal: JAMA (1975)

Laboratory evidence of recent or current lymphocytic choriomeningitis (LCM) virus infection was obtained in 60 patients. Twelve had diagnoses of central nervous system (CNS) infection: four of meningoencephalitis and eight of meningitis. Thirty-four patients had a grippe-like syndrome. Fifty-nine had had contact with pet hamsters. All of the 24 patients whose pets were studied had been exposed to one or more hamsters with serologic evidence of past LCM virus infection. The data implicate pet hamsters as a source of LCM in man. A continuous effective control of LCM virus in pet hamsters appears impractical. At present, the only feasible way to prevent further cases is the physician's special attention to the possibility of rodent contacts of patients with CNS disease and early laboratory confirmation of suspected cases of human LCM virus infections. (<i>JAMA</i>232:501-504, 1975)
Comparative Analysis of Breast Cancer (BrCa) Mortality Reduction among Regions of Canada between 1950 – 2004: Impact of Systemic and Diagnostic Guidelines after 1977, with Model Definition of Number of Potentially Avoided Annual Deaths (N-PAAD).
Authors: J. Ragaz, H. Wong, H. Qian
Journal: Cancer Research (2009)

Abstract BACKGROUNDWe reported in the past the BrCa mortality trends in three Provinces of Canada with different Levels of Provincial Diagnostic and Therapy Guideline (ProvDgThGuide) implementation, reflecting access to optimum cancer care (LEVEL I, most uniform: British Columbia (B.C.); LEVEL II, medium: Ontario(ON); LEVEL III, least uniform (Atlantic Provinces AP), and have shown best outcomes in B.C. (Cancer Res 2009 69[S] 2:383).OBJECTIVETo estimate the number of BrCa deaths that potentially could have been avoided during the period 1978 – 2004 if the ProvDgThGuide Level I (i.e. of B.C.) had been implemented in Canada, Ontario and Atlantic Provinces, respectively.METHODSData were obtained from Statistics Canada.i. For each region, we calculated the average annual age-standardized mortality rate / 100,000 (aveASR) for the periods 1950-1977 (R1) and 1978-2004 (R2).ii. Subsequently, calculated was the Relative Change (RC, expressed in %) in mortality rate between the two time periods (RC = (R2-R1)/R1).iii. And for each region, the 1978 – 2004 expected rates (RE) based on RC from B.C. [i.e. calculated as "-13.8%" [(RE = 1- 0138) x R1].iv. These steps permitted estimates of Number of potentially avoided [annual] deaths (N-PAAD), based on the difference in observed mortality during the 1978-2004 period and the mortality that would have occurred if the regions had experienced the same relative change in mortality rate as observed in B.C. (R2-RE x # at risk).RESULTS R1(aveASR 1950-1977)R2(aveASR 1978-2004)RCREN-PAAD(N-AveAnnDeaths)BC30.025.8-13.8%----Ontario30.929.2-5.3%26.6137Atlantic27.528.8+4.7%23.760Canadaexcluding BC30.729.0-5.5%26.5315CONCLUSIONThis study confirms in most but not all regions of Canada a substantial mortality reduction after 1977, suggestive that implementation of optimum levels of Provincial Diagnostic and Therapy Guidelines (optimum access to cancer care) may affect mortality, and that their delay may prevent materialization of survival gains.Once the average annual rates of B.C. was applied to the rates of rest of Canada, the newly developed "Potentially Avoided Annual Deaths" model estimates over 8,000 avoided BrCa deaths in Canada (without B.C.) during the period 1978 – 2004 (26 [years] x 315).The model estimates over 3,500 (26 x 137) and 1500 (26 x 60) avoided deaths, respectively, for Ontario and Atlantic Provinces.These data are relevant to all world regions with differing access to optimum cancer care. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2063.
Culture Clash: Law and Science in America
Authors: Frank T. Flannery
Journal: JAMA (1995)

In the author's view, America embraces science as an objective process, which evaluates theories on the basis of standard criteria. Through science, systematic experimentation yields reproducible results, and brilliance is manifested by doing something that no one has done before. Scientists build upon their predecessors' accomplishments. In this continuum, each successive advance is made possible by the prior work of others, but individual achievement is easily recognized. Moreover, there is universal agreement that scientific progress benefits the commonwealth. While science deals with knowledge of the natural world, law seeks to peacefully resolve human disputes through the application of a defined process. In the course of this dispute resolution, social goals are often accommodated and championed. The legal process is more time sensitive than scientific endeavors, and events often dictate a decision before the receipt of all objective data. The legal rules that are used are crafted by appellate judges who
Australian cervical cancer vaccination leads to rapid decline in genital warts
Authors: Z. Kmietowicz
Journal: BMJ (2009)

The number of young women presenting with new cases of genital warts in Australia has declined rapidly since the introduction of the national vaccination programme against cervical cancer, in 2007, research has found ( Sex Transm Infect 2009; doi:10.1136/sti.2009.037788).

The retrospective study, which looked at rates of genital warts among people attending a sexual health centre in Melbourne between January 2004 and December 2008, found new diagnoses among women under 28 years fell by 25% each quarter in …
Psychosocial determinants of outcomes in knee replacement
Authors: Maria A Lopez-Olivo, Glenn C Landon, Sherwin J Siff, David Edelstein, Chong Pak, Michael A Kallen, Melinda Stanley, Hong Zhang, Kausha C Robinson, Maria E Suarez-Almazor
Journal: Annals of the Rheumatic Diseases (2011)

To identify potential psychosocial and educational barriers to clinical success following knee replacement.The authors evaluated 241 patients undergoing total knee replacement, preoperatively and 6 months after surgery. Outcomes included the Western Ontario McMaster (WOMAC) scale and the Knee Society rating system (KSRS). Independent variables included: the medical outcome study-social support scale; depression, anxiety and stress scale; brief COPE inventory; health locus of control; arthritis self-efficacy scale and the life orientation test-revised. Multiple regression models evaluated associations of baseline demographic and psychosocial variables with outcomes at 6 months, controlling for body mass index, comorbidities and baseline outcome scores.Patients' mean age was 65 ± 9 years; 65% were women. Most patients improved outcomes after surgery. Several psychosocial variables were associated with outcomes. Regression analyses indicated lower education, less tangible support, depression, less problem-solving coping, more dysfunctional coping, lower internal locus of control were associated with worse WOMAC scores (R(2) contribution of psychosocial variables for pain 0.07; for function, 0.14). Older age, lower education, depression and less problem-solving coping were associated with poorer total KSRS scores (R(2) contribution of psychosocial variables to total KSRS model 0.09). Psychosocial variables as a set contributed from 25% to 74% of total explained variance across the models tested.Patients' level of education, tangible support, depression, problem-solving coping, dysfunctional coping and internal locus of control were associated with pain and functional outcomes after knee replacement. The findings suggest that, in addition to medical management, perioperative psychosocial evaluation and intervention are crucial in enhancing knee replacement outcomes.
The Plutonium Controversy
Authors: John W. Gofman
Journal: JAMA (1976)

IF THE world chooses to seek a solution to the energy dilemma through nuclear energy, the element plutonium will become an article of commerce to be handled in quantities of thousands of tonnes annually. Plutonium is a uniquely potent inhalation carcinogen, the potential induction of lung cancer dwarfing other possible toxic effects. For reasons to be presented here, it is my opinion that plutonium's carcinogenicity has been very seriously underestimated. If one couples the corrected carcinogenicity with the probable degree of industrial containment of the plutonium, it appears that the commercialization of a plutonium-based energy economy is not an acceptable option for society. Sagan's statement<sup>1</sup>that "the experience of 30 years supports the contention that plutonium can be used safely" is manifestly indefensible. No meaningful epidemiological study of plutonium-exposed workers for that 30-year period has ever been done. Since thousands of those possibly exposed have left the industry and are
TCT-579 Impact of diabetes mellitus on vascular healing after sirolimus eluting stent implantation; an optical coherence tomography study
Authors: Hoyoun Won, Byeong-Keuk Kim, Dong-Ho Shin, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Yang soo Jang, Myeong-Ki Hong
Journal: Journal of the American College of Cardiology (2013)
Alcohol and the heart: biochemical alterations
Authors: V.R. Preedy, V.B. Patel, H.J.F. Why, J.M. Corbett, M.J. Dunn, P.J. Richardson
Journal: Cardiovascular Research (1996)

A considerable amount of attention has focused on the cardiovascular events associated with ethanol consumption. The available evidence suggests that moderate ethanol consumption is associated with reduced risk of coronary heart disease, i.e., vessel events. In contrast, this review is primarily concerned with ethanol and heart muscle damage. Clinical features of the consequences of prolonged and excessive ethanol consumption encompass defects in myocardial contractility and derangement of cellular architecture, including disarray of the contractile elements. Although the incidence of heart muscle abnormalities in alcohol misusers is generally higher than previously considered, the mechanisms are only just being elucidated. This process has been facilitated by laboratory based studies in which animals receive either a single dose of ethanol (acute studies) or a continuous supply of ethanol in their daily diets (chronic studies). Results from these models show that acute ethanol dosage causes a marked decrease in the synthesis of contractile proteins. This occurs in the absence of overt mitochondrial abnormalities: ATP concentrations are generally unaffected. Paradoxically, the synthesis of mitchondrial proteins is reduced. Use of metabolic inhibitors suggests that the deleterious effects of acetaldehyde contribute to these reductions in protein synthesis. In chronic studies, ethanol causes a reduction in the amount of contractile proteins, and two dimensional protein profiling implicates selective loss of individual myocardial proteins. The differential activities of lysosomal proteases may contribute to this patterned response. However, in chronic ethanol feeding, adaptive mechanisms also become important, as the synthesis of the myofibrillary proteins increases. Overall, the mechanisms inherent in these biochemical responses may contribute to the genesis of a distinct disease entity, alcoholic heart muscle disease.
Calcium Uptake Activity of Canine Myocardial Sarcoplasmic Reticulum in the Presence of Anesthetic Agents
Authors: RICHARD F. LAIN, MICHAEL L. HESS, EDWARD W. GERTZ, F. NORMAN BRIGGS
Journal: Circulation Research (1968)

The anesthetics chloroform, halothane, ethyl ether, and sodium pentobarbital, which have negative inotropic properties, were examined for effects on the calcium pump of the sarcoplasmic reticulum of the dog myocardium. Chloroform and sodium pentobarbital, at concentrations similar to those depressing cardiac contractility, inhibited calcium uptake. The concentration of halothane required to inhibit calcium uptake was ten times greater than that required to produce depression of contractility. Ether at concentrations eight times greater than those producing inhibition of contraction was completely without effect on calcium uptake. Chloroform and halothane depressed calcium uptake and calcium-stimulated ATPase activity in parallel, indicating that these agents do not uncouple transport from ATP hydrolysis. Sodium pentobarbital, in contrast, uncoupled transport from ATP hydrolysis.
312 IKK/NF-KB SYSTEM PROTECTS FROM HEPATITIS B SURFACE ANTIGEN-INDUCED HEPATOCARCINOGENESIS
Authors: Y. Sunami, E. Kokai, F. Leithäuser, P. Riedl, C. Brunner, S. Gul, R. Schirmbeck, P. Strnad, T. Wirth
Journal: Journal of Hepatology (2012)
Preterm rupture of the membranes
Authors: M. Thiery
Journal: BMJ (1982)

bone structure is directly related to the stresses imposed on bone.1 Later he proposed that all changes in the function of bones are attended by definite alterations in their internal architecture.2This became known as Wolff's law-a law which can be restated in more general terms as: "The law of use and disuse."Use leads to hypertrophy, and disuse leads to atrophy.Bone mass and bone metabolism are relatively easy to measure, and Wolff's law as applied to bone has been repeatedly verified.It has been shown that both the action of gravity and the stresses of muscles and tendons are necessary for the maintenance of bone mass.Thus we all know that calcium drains out of bones of patients
Sodium pump inhibition, enhanced calcium influx via sodium-calcium exchange, and positive inotropic response in cultured heart cells.
Authors: W H Barry, Y Hasin, T W Smith
Journal: Circulation Research (1985)

The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydroouabain, 5 X 10(-5)M, and extracellular potassium of 1.0 mM all induced similar and prominent positive inotropic effects. These effects were accompanied, in each case, by 40-50% inhibition of the rate of active uptake of 42K and by similar increases in steady state sodium content. Stimulation of the rate of 45Ca uptake on exposure to zero extracellular sodium occurred in response to extracellular potassium (1.0 mM) or to glycoside concentrations that induced a positive inotropic effect and sodium-potassium pump inhibition. Reactivation of the sodium pump after return from 1.0 to 4.0 mM extracellular potassium was rapid and was associated with membrane hyperpolarization and slowing of spontaneous beating rate. With pump reactivation under these circumstances, the time course of disappearance of stimulation of sodium-calcium exchange on exposure to zero extracellular sodium was similar to the time course of loss of the positive inotropic effect. Under physiological conditions (4.0 mM extracellular potassium), exposure to positively inotropic but nontoxic concentrations of ouabain or dihydroouabain caused a small but consistent increase in unidirectional calcium influx, but had no discernible effect on calcium efflux. Since similar inotropic effects were produced for comparable degrees of glycoside or low extracellular potassium-induced sodium pump inhibition and increases in cellular sodium content, sodium pump inhibition rather than a glycoside-specific change in calcium binding appears to underlie the inotropic response. These findings are further consistent with the view that the primary mechanism of the positive inotropic effects of digitalis and low extracellular potassium in this experimental preparation is sodium pump inhibition resulting in increased intracellular sodium. We suggest that increased calcium influx via sodium-calcium exchange is the principal mechanism whereby increased intracellular sodium results in enhanced calcium availability to the myofibrils, but an additional effect on calcium efflux is not excluded.