tbuckley/cabot-search huggingface dataset:
Brain mechanisms of acoustic communication in humans and nonhuman primates: An evolutionary perspective
Authors: Hermann Ackermann, Steffen R. Hage, Wolfram Ziegler
Journal: Behavioral and Brain Sciences (2014)

Any account of "what is special about the human brain" (Passingham 2008) must specify the neural basis of our unique ability to produce speech and delineate how these remarkable motor capabilities could have emerged in our hominin ancestors. Clinical data suggest that the basal ganglia provide a platform for the integration of primate-general mechanisms of acoustic communication with the faculty of articulate speech in humans. Furthermore, neurobiological and paleoanthropological data point at a two-stage model of the phylogenetic evolution of this crucial prerequisite of spoken language: (i) monosynaptic refinement of the projections of motor cortex to the brainstem nuclei that steer laryngeal muscles, presumably, as part of a "phylogenetic trend" associated with increasing brain size during hominin evolution; (ii) subsequent vocal-laryngeal elaboration of cortico-basal ganglia circuitries, driven by human-specific FOXP2 mutations.;>This concept implies vocal continuity of spoken language evolution at the motor level, elucidating the deep entrenchment of articulate speech into a "nonverbal matrix" (Ingold 1994), which is not accounted for by gestural-origin theories. Moreover, it provides a solution to the question for the adaptive value of the "first word" (Bickerton 2009) since even the earliest and most simple verbal utterances must have increased the versatility of vocal displays afforded by the preceding elaboration of monosynaptic corticobulbar tracts, giving rise to enhanced social cooperation and prestige. At the ontogenetic level, the proposed model assumes age-dependent interactions between the basal ganglia and their cortical targets, similar to vocal learning in some songbirds. In this view, the emergence of articulate speech builds on the "renaissance" of an ancient organizational principle and, hence, may represent an example of "evolutionary tinkering" (Jacob 1977).
Liver Transplantation
Authors: Thomas E. Starzl, Anthony J. Demetris, David Van Thiel
Journal: New England Journal of Medicine (1989)

(First of Two Parts)ADVANCES in the management of both chronic and acute hepatic disease have been made possible and even mandated by the development of liver transplantation. The clinical use of transplantation has proceeded at a rapid pace since a Consensus Development Conference of the National Institutes of Health concluded in June 1983 that liver transplantation had become a service and not simply an experimental procedure.1 The liver can be transplanted as an extra (auxiliary) organ at an ectopic site, or in the orthotopic location after the removal of the host liver (Fig. 1). This article will focus primarily . . .
Intravascular ultrasound of renal arteries in patients undergoing percutaneous transluminal angioplasty: Feasibility, safety and initial findings, including 3 dimensional reconstruction of renal arteries
Authors: Kenneth Rosenfield, Douglas W. Losordo, Michael Harding, Ann Pieczek, James Waters, Jeffrey M. Isner
Journal: Journal of the American College of Cardiology (1991)
Stem cell gene transfer—efficacy and safety in large animal studies
Authors: Peter A. Horn, Julia C. Morris, Tobias Neff, Hans-Peter Kiem
Journal: Molecular Therapy (2004)

The tremendous potential of stem cell-directed gene therapy has recently been demonstrated with the cure of children suffering from X-linked severe combined immunodeficiency (X-SCID) and adenosine deaminase deficiency [1–3]. A new era of medicine appeared to be on the horizon, but enthusiasm was quickly dampened after it became evident that this clinical success had not come without severe adverse events (SAEs). Unfortunately, 2 of 10 children treated with gene therapy developed leukemia [4,5]. Thus, the very study that was initially regarded as the breakthrough for stem cell gene therapy is now considered by some as the breakdown for the field.
Abstract A30: Dysregulation of BMI1 and microRNA-16 collaborate to enhance an anti-apoptotic potential in the side population of refractory mantle cell lymphoma
Authors: Akihiro Kitadate, Kazuaki Teshima, Kouichi Ohshima, Masao Seto, Kenichi Sawada, Hiroyuki Tagawa
Journal: Cancer Research (2013)

Abstract The proto-oncogene BMI1 and its product, Bmi1, is overexpressed in various types of tumors, particularly in aggressive tumors and tumors resistant to conventional chemotherapy. BMI1/Bmi1 is also crucially involved in cancer-initiating cell maintenance, and is recurrently upregulated in mantle cell lymphoma (MCL), especially aggressive variants. Recently, side population (SP) cells were shown to exhibit tumor-initiating characteristics in various types of tumors. In this study, we show that recurrent MCL cases significantly exhibit upregulation of BMI1/Bmi1. We further demonstrate that clonogenic MCL SP shows such tumor-initiating characteristics as high tumorigenicity and self-renewal capability, and that BMI1 was upregulated in the SP from recurrent MCL cases and MCL cell lines. On screening for upstream regulators of BMI1, we found that expression of microRNA-16 (miR-16) was downregulated in MCL SP cells by regulating Bmi1 in the SPs, leading to reductions in tumor size following lymphoma xenografts. Moreover, to investigate downstream targets of BMI1 in MCL, we performed cross-linking/chromatin immunoprecipitation assay against MCL cell lines and demonstrated that Bmi1 directly regulated pro-apoptotic genes such as BCL2L11/Bim and PMAIP1/Noxa, leading to enhance anti-apoptotic potential of MCL. Finally, we found that a proteasome inhibitor bortezomib, which has been recently used for relapsed MCL, effectively induced apoptosis among MCL cells while reducing expression of Bmi1 and increasing miR-16 in MCL SP. These results suggest that upregulation of BMI1 and downregulation of miR-16 in MCL SP has a key role in the disease's progression by reducing MCL cell apoptosis. Our results provide important new insight into the pathogenesis of MCL and strongly suggest that targeting BMI1/Bmi1 might be an effective approach to treating MCL, particularly refractory and recurrent cases. Citation Format: Akihiro Kitadate, Kazuaki Teshima, Kouichi Ohshima, Masao Seto, Kenichi Sawada, Hiroyuki Tagawa. Dysregulation of BMI1 and microRNA-16 collaborate to enhance an anti-apoptotic potential in the side population of refractory mantle cell lymphoma. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A30.
Demonstration of training effect during chronic beta-adrenergic blockade in patients with coronary artery disease.
Authors: C M Pratt, D E Welton, W G Squires, T E Kirby, G M Hartung, R R Miller
Journal: Circulation (1981)

Attenuation of exercise-induced increases in heart rate and cardiac output by chronic beta-adrenergic blockade has been thought to compromise benefit of exercise training in patients with coronary artery disease (CAD). To assess this important issue, 35 CAD patients were evaluated by a 3-month walk-jog-cycle training program: 14 patients received no beta blocker (group 1), 14 received propranolol, 30-80 mg/day (group 2), and seven patients received propranolol, 120-240 mg/day (group 3). The extent of CAD, resting heart rate before training blood pressure and VO2 max were similar (p = NS) in each group. The maximal exercise heart rate (mean +/- SD, 147 +/- 21 beats/min in group 1 vs 120 +/- 10 beats/min in group 2 and 115 +/- 12 beats/min in group 3 (both p less than 0.05 vs group 1). The VO2 max before training was 25 +/- 5.0 ml/kg/min in group 1 vs 23 +/- 3.2 ml/kg/min in group 2 and 26 +/- 2.8 ml/Kg/min in group 3 (all p = NS). Training consisted of three 1-hour periods per week at a heart rate of 70-85% of the maximal pretraining heart rate. In each group, VO2 increased (p less than 0.05) after training: group 1, 27%; group 2, 30%; group 3, 46%. The double product was unchanged after training (p = NS) in each group. These data indicate that substantial training effects may be achieved in CAD patients despite therapeutic doses of beta blockers and a reduced training HR. Thus, there appears to be no indication to reduce beta blockers in CAD patients engaged in cardiac rehabilitation.
Cultural and Economic Factors That (Mis)Shape Antibiotic Use: The Nonpharmacologic Basis of Therapeutics
Authors: Jerry Avorn
Journal: Annals of Internal Medicine (2000)

The use of antibiotics in both ambulatory and inpatient settings is heavily shaped by cultural and economic factors as well as by microbiological considerations. These nonpharmacologic factors are relevant to clinicians and policymakers because of the clinical and fiscal toll of inappropriate antibiotic prescribing, including excessive use, preventable adverse effects, and the increasing prevalence of resistant organisms. An understanding of the determinants of antibiotic consumption is critical to explain current patterns of use and to devise programs to reduce inappropriate use. Patient motivations include the desire for a tangible product of the clinical encounter coupled with incorrect perceptions of the effectiveness of antibiotics, particularly in viral infections. Physician behavior can be explained by such factors as lack of information, a desire to satisfy patient demand, and pressure from managed care organizations to speed throughput. Marketing campaigns directed at both physicians and patients further serve to increase demand, especially for newer, costlier products. Studies of antibiotic use patterns in inpatient and outpatient care consistently demonstrate considerable inappropriate prescribing, which is likely to exacerbate the emergence of resistant organisms. Several approaches have been shown to improve the rationality of antibiotic use. Computer-based algorithms or reminders can prompt physicians to improve antibiotic choices at the time of prescribing; paper-based order entry forms can achieve the same goal. Interactive educational outreach ("academic detailing") is a practical implementation of social marketing principles to improve antibiotic use. Public education programs directed at consumers can help to reduce the inappropriate patient demand that helps to drive much improper antibiotic prescribing.
A1.72 Baricitinib, an oral janus kinase inhibitor, in the treatment of rheumatoid arthritis: safety and efficacy in an open-label, long-term extension study<sup>1</sup>
Authors: Peter Taylor, Mark Genovese, Ed Keystone, Douglas Schlichting, Scott Beattie, William Macias
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Baricitinib (formerly LY3009104/INCB028050) is a novel, oral inhibitor of JAK1 and JAK2 in the JAK-STAT signalling pathway being investigated as a treatment for rheumatoid arthritis (RA). <h3>Objectives</h3> To report 52 week safety and efficacy findings of an open label extension of the phase 2b study. <h3>Methods</h3> Patients (Pts) were initially randomised to placebo (PBO) or 1of 4 once-daily (QD) baricitinib doses (1, 2, 4, or 8 mg) for 12 wks. Pts assigned to 2 mg, 4 mg or 8 mg continued assigned treatment and pts assigned to placebo or 1 mg were reassigned to 4 mg QD or 2 mg BID for an additional 12 weeks of blinded treatment. In the open label portion of the study, patients in 8 mg group continued to receive 8 mg QD and all other patients received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at the investigator's discretion when &gt;6 tender and swollen joints were present. Analyses reported here include data through 52 weeks for patients treated in the open-label extension (non-responder imputation used for discontinued patients). <h3>Results</h3> Of the 212 pts eligible to participate, 201(95%) pts entered the open label extension, 184 patients completed 52 weeks of treatment, 15 pts discontinued, and 2 pts had not yet completed 52 weeks. Among pts who remained on 4 mg (n = 108), TEAEs occurred in 57 (53%), SAEs in 14 (13%), infections in 34 (31%) and serious infections in 4 (4%). Among pts who received 8 mg at any time (n = 93), TEAEs occurred in 59 (63%), SAEs in 8 (9%), infections in 37 (40%) and serious infections in 2 (2%). No opportunistic infections or TB cases were observed. There was one death due to myocardial infarction in the 8 mg group. Among all patients combined in the open label extension, the proportions of pts achieving ACR20, ACR50, ACR70, CDAI Remission, SDAI Remission, DAS28CRP ≤3.2, DAS28CRP &lt;2.6, DAS28ESR ≤3.2, DAS28CRP &lt;2.6 or the ACR/EULAR Boolean remission at the start of the open label extension (week 24) were similar or increased at week 52 (Table). <h3>Conclusions</h3> Among pts completing 52 weeks of a phase 2b study, clinical improvements observed at week 24 were maintained or improved during the open label extension. Safety signals observed over the open label extension were consistent with previously reported results of baricitinib. <h3>Reference</h3> 1.1. EULAR 2013, <i>Ann Rheum Dis</i> 2013;72 Supplement 3:65, Genovese et al.
Induction of heparin-binding epidermal growth factor-like growth factor mRNA by protein kinase C activators
Authors: Mian-Shin Tan, Jer-Chia Tsai, Yau-Jiunn Lee, Hung-Chun Chen, Shyi-Jang Shin, Yung-Hsiung Lai, Mark A. Perrella, Cesario Bianchi, Shigeki Higashiyama, Wilson Endege, Mu-En Lee, Juei-Hsiung Tsai
Journal: Kidney International (1994)
Assessing the Incidence of Ciguatera Fish Poisoning with Two Surveys Conducted in Culebra, Puerto Rico, during 2005 and 2006
Authors: Eduardo Azziz-Baumgartner, George Luber, Laura Conklin, Thomas R. Tosteson, Hudson R. Granade, Robert W. Dickey, Lorraine C. Backer
Journal: Environmental Health Perspectives (2012)

Although ciguatera fish poisoning (CFP) is the most common seafood intoxication worldwide, its burden has been difficult to establish because there are no biomarkers to diagnose human exposure.
Peritoneal Dialysis for Pulmonary Oedema After Acute Myocardial Infarction
Authors: M. P. Chopra, R. B. Gulati, R. W. Portal, C. P. Aber
Journal: BMJ (1970)

Four patients with intractable pulmonary oedema after acute myocardial infarction were treated with peritoneal dialysis. A negative fluid balance was rapidly achieved in three patients, two of whom ultimately survived. The fourth patient, who had complete heart block at the beginning of dialysis, showed initial clinical improvement with restoration of sinus rhythm despite failure to extract fluid.
THE ORIGIN OF URINARY PROTEINS
Authors: EDMUND ANDREWS
Journal: JAMA (1928)

In a recent communication<sup>1</sup>it was shown that uremia could be reproduced in its minutest details in the presence of normal kidneys. Suppression of urine was previously shown to occur, not because the kidneys became impermeable but because the water was held in a firmer combination with the colloids of the blood and tissues.<sup>2</sup>The nitrogen retention cannot be the cause of nephritic syndromes, as many cases of uremia in which the blood nitrogen values were normal have been reported in the recent literature. Again, suppression of urinary excretion per se for very long periods (over three weeks) has not caused uremic manifestations either experimentally or clinically. With these points in view the urinary proteins were studied not only in cases of experimental uremia but in ether nephritides in dogs. Small samples were collected every ten to fifteen minutes, and each sample that contained protein was tested against
Patients' Understanding About Drugs
Authors: Raulo S. Frear
Journal: JAMA (1987)

<h3>To the Editor.—</h3> I have read with considerable interest the article entitled "The Impact of a Drug Information Sheet on the Understanding and Attitude of Patients About Drugs" by Johnson et al.<sup>1</sup>Unfortunately, an important piece of information is absent from the description of the study groups. Specifically, in Table 1 we are given no comparison of the A and B groups for either the inpatient or outpatient study groups. Without that information, I am hard pressed to make any conclusions about the relative usefulness of such a program. To me, however, there are more important questions. Where was the pharmacist? Training patients to understand their drug therapy may be the single most effective way to decrease misuse of prescription as well as nonprescription medications. Nowhere in the spectrum of patient care is the need to utilize the pharmacist, the health care team's drug therapy expert, more apparent than
An anemic patient with phenotypical ?-thalassemic trait has elevated level of structurally normal ?-globin mRNA in reticulocytes
Authors: Sai-Kiang Lim, Azhar bin Ali, Hai Yang Law, Ivy Ng, Maxey Chung Ming Chung, Szu-Hee Lee
Journal: American Journal of Hematology (2000)

Of the numerous β-thalassemic mutations linked or unlinked to the β-globin gene, all invariably cause a decrease in or an absence of structurally normal β-globin mRNA when assayed. Here we report an anemic patient with an elevated α-/β globin synthesis ratio of 2.0 in his reticulocytes. The patient's blood film showed marked red cell anisopoikilocytosis, microcytosis, and hypochromia, consistent with a typical β-thalassemic trait phenotype. Acid-eluted erythrocytes contained numerous Heinz bodies. Molecular analysis of the patient's reticulocyte mRNA indicated that, compared to normal controls, there was a 3-fold elevation of β-globin mRNA when assayed by RT-PCR and a 1.5-fold elevation of β-globin mRNA when assayed by RNA slot blotting. The level of α-globin mRNA was normal when compared to that of normal adult controls. Extensive structural analysis of the β-globin mRNA and gene by sequencing of RT-PCR and PCR products, respectively, did not detect any mutations. Tryptic mapping of purified β-globin chains also did not show any abnormal tryptic fragments. These data indicated that a relative insufficiency of structurally normal β-globin mRNA was not a cause of this β-thalassemic phenotype. Therefore, the lesion that caused this particular thalassemic phenotype is not linked to the β-globin allele. Am. J. Hematol. 65:243–250, 2000. © 2000 Wiley-Liss Inc.
Direct and reflex effects of nitroglycerin on coronary and left ventricular dynamics in conscious dogs
Authors: Stephen F. Vatner, Charles B. Higgins, Ronald W. Millard, Dean Franklin
Journal: Journal of Clinical Investigation (1972)

The effects of intravenous and sublingual glyceryl trinitrate (nitroglycerin), 40 mug/kg, were studied on coronary blood flow and resistance, left ventricular (LV) pressures (P) and diameters (D), rate of change of pressure (dP/dt), (dP/dt)/P, and on the velocity (V) of myocardial fiber shortening in conscious dogs. Nitroglycerin i.v. caused substantial coronary vasodilatation prior to any changes in systemic hemodynamics. Mean coronary flow increased by a maximum of 47 ml/min and coronary sinus P(o2) rose from 16 to 26 mm Hg while pressure and diameter began to fall, and heart rate began to rise. After the maximal fall in mean arterial pressure (-26 mm Hg), a secondary peak in coronary flow occurred which was associated with increases in heart rate (100 beats/min), (dP/dt)/P (22%), and isolength V (12%). Beta blockade prevented the reflex increases in contractility but only a part of the reflex tachycardia; the remainder was prevented by cholinergic blockade. Maintaining heart rate constant minimized the decreases in LV D and increases in contractility. When the reflex inotropic and chronotropic effects were prevented by a combination of atrial pacing and beta blockade the early coronary vasodilatation was unaltered, but the later coronary vasodilatation was minimized. Thus i.v. nitroglycerin in the conscious dog exerts a potent direct coronary vasodilating action and also a secondary coronary vasodilation caused by reflex increases in contractility and heart rate. The decreases in diameter are largely the result of tachycardia. Sublingual nitroglycerin produced directionally similar, but quantitatively lesser effects on coronary flow and resistance, LV D, LV P, and contractility.
Hazards of Drug Dependency
Authors: Donald V. Hirst
Journal: JAMA (1972)

<h3>To the Editor.—</h3> In his article "Hazards of Drug Dependency" (<b>218</b>:1533, 1971) Little mentions the terms, "inner spasm," "tension," and "tense depression" without defining them. Perhaps he knew he didn't have to define them. Emotional tensions are a universal human experience, and, in addition, the human need to reduce or abolish painful tensions is also universal. The literature does not give satisfactory definitions and descriptions of emotional tensions. Because I am a primary care physician and treat unscreened, unreferred, indigenous patients and because at least two out of three such patients are in emotional and physical difficulties with painful tensions, it has been absolutely necessary to find some answers, explanations, and methods of treatment for these patients. Painful tensions are basically alarm tensions which mobilize the body to fight and run from actual danger—the emergency or alarm state. Acute alarm in the face of danger is normal, but chronic
Dexamethasone modulates lipoprotein metabolism in cultured human monocyte-derived macrophages. Stimulation of scavenger receptor activity.
Authors: L J Hirsch, T Mazzone
Journal: Journal of Clinical Investigation (1986)

Human monocyte-derived macrophages (HMM) play a key role in the formation of atherosclerotic plaques by accumulating cholesteryl ester (CE) to become foam cells. HMM have receptors for native low density lipoprotein (LDL) and acetylated-LDL (ALDL), and uptake of ALDL can promote substantial cellular CE accumulation. Furthermore, macrophages specifically and saturably bind glucocorticoids, which in turn modulate numerous macrophage functions. Preincubating HMM in dexamethasone-inhibited LDL degradation (230 +/- 12 vs. 515 +/- 21 ng/mg cell protein X 18 h, P less than 0.001) but stimulated ALDL degradation (5.3 +/- 0.5 vs. 2.5 +/- 0.3 micrograms/mg X 18 h, P less than 0.01). These effects were time- and dose-dependent, occurring maximally by 24 h and with 2.5 X 10(-8) M dexamethasone. Dexamethasone increased the maximum velocity for ALDL degradation (16.2 vs. 12.0 micrograms/mg X 18 h, P less than 0.01) without changing the apparent Michaelis constant. Progesterone, 11 alpha-epicortisol, and 17 alpha-OH progesterone (a competitive antagonist of the glucocorticoid receptor) had no effect on HMM ALDL degradation, but 17 alpha-OH progesterone abolished the stimulatory action of dexamethasone. In he presence of ALDL, incorporation of [14C]oleic acid into CE was enhanced over fourfold by dexamethasone (4015 +/- 586 vs. 943 +/- 91 cpm/mg X 2 h, P less than 0.01), and HMM incubated with ALDL and dexamethasone accumulated more free cholesterol (34.6 +/- 1.9 vs. 26.2 +/- 0.8 micrograms/mg, P less than 0.02) and CE (32.8 +/- 2.3 vs. 14.8 +/- 0.8 micrograms/mg, P less than 0.002) than did macrophages without dexamethasone. In cultured human umbilical vein endothelial cells, dexamethasone did not change ALDL degradation, but reduced LDL degradation by 30% (P less than 0.001). In summary, dexamethasone inhibits LDL receptor activity by both macrophages and endothelial cells, but stimulates ALDL receptor activity only in macrophages. These observations provide evidence for the regulation of macrophage endocytic receptors by glucocorticoid hormones.