tbuckley/cabot-search huggingface dataset:
Enzymatic amplification of platelet-specific messenger RNA using the polymerase chain reaction.
Authors: P J Newman, J Gorski, G C White, S Gidwitz, C J Cretney, R H Aster
Journal: Journal of Clinical Investigation (1988)

Human platelets are derived from megakaryocytes as anucleate cells, and thus contain only vestigial amounts of RNA capable of being transcribed into protein. This has greatly hampered efforts to study directly platelet-specific gene products and their associated polymorphisms. In this report, we describe direct amplification, using the polymerase chain reaction, of platelet-derived mRNA in amounts sufficient to permit detailed analysis, such as restriction mapping and nucleotide sequencing. The ability to generate large amounts of cDNA from platelet-specific mRNA sequences should make possible direct molecular characterization of normal platelet proteins, and facilitate the investigation of a wide variety of inherited platelet disorders.
The Psychiatric Interview: The Impact of the First Three Minutes
Authors: MYRON G. SANDIFER, ANTHONY HORDERN, LINDA M. GREEN
Journal: American Journal of Psychiatry (1970)

In a two-phase study of diagnostic decision making, psychiatrist observers viewed films of diagnostic interviews and recorded their comments and the symptoms they saw in the patients. Analysis of the results, in terms of the time at which conclusions and symptoms were reported, revealed that the first three minutes of observation have a significant, and sometimes apparently decisive, impact upon the final diagnostic decision.
The Ethics of Contacting Family Members of a Subject in a Genetic Research Study to Return Results for an Autosomal Dominant Syndrome
Authors: Holly A. Taylor, Benjamin S. Wilfond
Journal: The American Journal of Bioethics (2013)

This case explores the ethical landscape around recontacting a subject's relatives to return genetic research results when the informed consent form signed by the original cohort of subjects is silent on whether investigators may share new information with the research subject's family. As a result of rapid advances in genetic technology, methods to identify genetic markers can mature during the life course of a study. In this case, the investigators identified the genetic mutation responsible for the disorder after a number of their original subjects had died. The researchers now have the ability to inform relatives of the subject about their risk of developing the same disease. Mark Rothstein, JD, from the University of Louisville School of Medicine, provides an overview of the medical/scientific, legal, and ethical issues underlying this case. Lauren Milner, PhD, and colleagues at Stanford University explore how the relationship between researcher and subject affect this debate. Seema Shah, JD, and colleagues at the National Institutes of Health and University of California, Los Angeles (UCLA) discuss whether and how requirements of the duty to warn are applicable in this case.
Electrophysiologic Effects of Acute Myocardial Ischemia
Authors: Robin M. Shaw, Yoram Rudy
Journal: Circulation Research (1997)

A multicellular ventricular fiber model was used to determine mechanisms of slowed conduction and conduction failure during acute ischemia. We simulated the three major pathophysiological component conditions of acute ischemia: elevated [K + ] o , acidosis, and anoxia. Elevated [K + ] o was the major determinant of conduction, causing supernormal conduction, depressed conduction, and conduction block as [K + ] o was gradually increased from 4.5 to 14.4 mmol/L. Only elevated [K + ] o caused conduction failure when varied within the range reported for acute ischemia. Before block, depressed upstrokes consisted of two distinct components: the first to the fast Na + current (I Na ) and the second to the L-type Ca 2+ current (I Ca(L) ). Even in highly depressed conduction, excitability was maintained by I Na , with conduction block occurring at 95% I Na inactivation. However, because I Ca(L) supported the later phase of the depressed upstroke, I Ca(L) enhanced conduction and delayed block by increasing the electrotonic source current. At [K + ] o =18 mmol/L, slow action potentials generated by I Ca(L) were obtained with 10% I Ca(L) augmentation. However, in the presence of acidosis and anoxia, significantly larger (120%) I Ca(L) augmentation was required. The depressant effect was due mostly to anoxic activation of outward ATP-sensitive K + current, which counteracts inward I Ca(L) and, by lowering the action potential amplitude, decreases the electrotonic current available to depolarize downstream cells. The simulations highlight the interactive nature of electrophysiological ischemic changes during propagation and demonstrate that both membrane changes and load factors (by downstream fiber) must be considered.
Interfering with capsid formation: A practicable antiviral strategy against hepatitis B virus?
Authors: Michael Kann, Hartmut Jaeschke, Kevin Mullen, Darius Moradpour
Journal: Hepatology (2004)

Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-α and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and the substantial resistance of the virus to nucleosidic inhibitors. Potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired. We describe nonnucleosidic inhibitors of HBV nucleocapsid maturation that possess in vitro and in vivo antiviral activity. These inhibitors have potential for future therapeutic regimens to combat chronic HBV infection.
Does robotic technology make minimally invasive cardiac surgery too expensive? A hospital cost analysis of robotic and conventional techniques
Authors: Jeffrey A. Morgan, Barbara A. Thornton, Karen W. Hollingsworth, Nicholas J. Colletti, Aftab R. Kherani, Deon W. Vigilance, Faisal H. Cheema, Eric A. Rose, Craig R. Smith, Mehmet C. Oz, Michael Argenziano
Journal: Journal of the American College of Cardiology (2003)
Is It Always True That ERCP Cannot Be Carried out in Patients with Roux-en-Y Gastrojejunostomy?
Authors: S. Mosco, G. Uomo, T. Ceglia, G. Galasso
Journal: Endoscopy (1998)

See also: Forward-Viewing Endoscope or Side-Viewing Duodenoscope for ERCP in Patients after Billroth II Gastrectomy?Endoscopy 1998; 30(01): 51-51DOI: 10.1055/s-2007-993730
Plasma exchange v peritoneal dialysis for removing Bence Jones protein.
Authors: J A Russell, B M Fitzharris, R Corringham, D A Darcy, R L Powles
Journal: BMJ (1978)

Plasma exchange v peritoneal dialysis for removing Bence Jones protein A major cause of renal failure in multiple myeloma is damage by light chains or Bence Jones protein (BJP).Serum BJP concentrations may
Aggravation by prostaglandin E2 of interleukin-6-dependent insulin resistance in hepatocytes
Authors: Janin Henkel, Frank Neuschäfer-Rube, Andrea Pathe-Neuschäfer-Rube, Gerhard P. Püschel
Journal: Hepatology (2009)

Hepatic insulin resistance is a major contributor to fasting hyperglycemia in patients with metabolic syndrome and type 2 diabetes. Circumstantial evidence suggests that cyclooxygenase products in addition to cytokines might contribute to insulin resistance. However, direct evidence for a role of prostaglandins in the development of hepatic insulin resistance is lacking. Therefore, the impact of prostaglandin E(2) (PGE(2)) alone and in combination with interleukin-6 (IL-6) on insulin signaling was studied in primary hepatocyte cultures. Rat hepatocytes were incubated with IL-6 and/or PGE(2) and subsequently with insulin. Glycogen synthesis was monitored by radiochemical analysis; the activation state of proteins of the insulin receptor signal chain was analyzed by western blot with phosphospecific antibodies. In hepatocytes, insulin-stimulated glycogen synthesis and insulin-dependent phosphorylation of Akt-kinase were attenuated synergistically by prior incubation with IL-6 and/or PGE(2) while insulin receptor autophosphorylation was barely affected. IL-6 but not PGE(2) induced suppressors of cytokine signaling (SOCS3). PGE(2) but not IL-6 activated extracellular signal-regulated kinase 1/2 (ERK1/2) persistently. Inhibition of ERK1/2 activation by PD98059 abolished the PGE(2)-dependent but not the IL-6-dependent attenuation of insulin signaling. In HepG2 cells expressing a recombinant EP3-receptor, PGE(2) pre-incubation activated ERK1/2, caused a serine phosphorylation of insulin receptor substrate 1 (IRS1), and reduced the insulin-dependent Akt-phosphorylation.PGE(2) might contribute to hepatic insulin resistance via an EP3-receptor-dependent ERK1/2 activation resulting in a serine phosphorylation of insulin receptor substrate, thereby preventing an insulin-dependent activation of Akt and glycogen synthesis. Since different molecular mechanisms appear to be employed, PGE(2) may synergize with IL-6, which interrupted the insulin receptor signal chain, principally by an induction of SOCS, namely SOCS3.
Recognition and Significance of Intraventricular Block due to Myocardial Infarction (Peri-infarction Block)
Authors: K. S. SHADAKSHARAPPA, J. M. KALBFLEISCH, L. L. CONRAD, N. K. SARKAR
Journal: Circulation (1968)

Evidence of peri-infarction block was found in 39% of the electrocardiograms of 1,938 patients with definite evidence of myocardial infarction. It most commonly occurred acutely or within several days following infarction and was more common with recurrent infarction. Peri-infarction block infrequently disappeared and was associated with higher values for serum glutamic-oxalacetic transaminase and a greater mortality in the first year following myocardial infarction. There was no autopsy correlation of peri-infarction block and ventricular aneurysmal formation. The term "peri-infarction block" is appropriate only when abnormal intraventricular conduction occurs in association with definite electrocardiographic evidence of myocardial infarction.
The Host Restriction Factor APOBEC3G and Retroviral Vif Protein Coevolve due to Ongoing Genetic Conflict
Authors: Alex A. Compton, Vanessa M. Hirsch, Michael Emerman
Journal: Cell Host & Microbe (2012)

SummaryAPOBEC3G (A3G) is a host cytidine deaminase that inhibits retroviruses. HIV and related primate lentiviruses encode Vif, which counteracts A3G by inducing its degradation. This Vif-mediated A3G inhibition is species specific, suggesting that the A3G-Vif interaction has evolved as primate lentiviruses have adapted to their hosts. We examined the evolutionary dynamics of the A3G-Vif interaction within four African green monkey (AGM) subspecies, which are each naturally infected with a distinct simian immunodeficiency virus (SIV). We identified single amino acid changes within A3G in two AGM subspecies that render it resistant to Vif proteins, except for Vif from the viruses that naturally infect these subspecies. Moreover, experimental infection of AGMs shows that Vif can rapidly adapt to these arising Vif-resistant A3G genotypes. These data suggest that despite being generally nonpathogenic in its natural host, SIV infection selects for Vif-resistant forms of A3G in AGM populations, driving Vif counterevolution and functional divergence.Highlights•SIV selects for variants of a restriction factor, Apobec3G, in its primate host•SIV adapts to polymorphism in Apobec3G through evolution of the viral gene, Vif•Lentiviruses thought to be nonpathogenic still cause selection in their natural host
Hemodynamic Effects of Long-Term Cardiac Resynchronization Therapy
Authors: Paul Steendijk, Sven A. Tulner, Jeroen J. Bax, Pranobe V. Oemrawsingh, Gabe B. Bleeker, Lieselot van Erven, Hein Putter, Harriette F. Verwey, Ernst E. van der Wall, Martin J. Schalij
Journal: Circulation (2006)

Acute hemodynamic effects of cardiac resynchronization therapy (CRT) were reported previously, but detailed invasive studies showing hemodynamic consequences of long-term CRT are not available.We studied 22 patients scheduled for implantation of a CRT device based on conventional criteria (New York Heart Association class III or IV, left ventricular [LV] ejection fraction <35%, left bundle-branch block, and QRS duration >120 ms). During diagnostic catheterization before CRT, we acquired pressure-volume loops using conductance catheters during atrial pacing at 80, 100, 120, and 140 bpm. Studies were repeated during biventricular pacing at the same heart rates after 6 months of CRT. Our data show a significant clinical benefit of CRT (New York Heart Association class change from 3.1+/-0.5 to 2.1+/-0.8; quality-of-life score change from 44+/-12 to 31+/-16; and 6-minute hall-walk distance increased from 260+/-149 to 396+/-129 m; all P<0.001), improved LV ejection fraction (from 29+/-10% to 40+/-13%, P<0.01), decreased end-diastolic pressure (from 18+/-8 to 13+/-6 mm Hg, P<0.05), and reverse remodeling (end-diastolic volume decreased from 257+/-67 to 205+/-54 mL, P<0.01). Previously reported acute improvements in LV function remained present at 6 months: dP/dtmax increased 18%, -dP/dtmin increased 13%, and stroke work increased 34% (all P<0.01). Effects of increased heart rate were improved toward more physiological responses for LV ejection fraction, cardiac output, and dP/dtmax. Moreover, our study showed improved ventricular-arterial coupling (69% increase, P<0.01) and improved mechanical efficiency (44% increase, P<0.01).Hemodynamic improvements with CRT, previously shown in acute invasive studies, are maintained chronically. In addition, ventricular-arterial coupling, mechanical efficiency, and chronotropic responses are improved after 6 months of CRT. These findings may help to explain the improved functional status and exercise tolerance in patients treated with CRT.
Uterine Perforation by Intrauterine Devices-Reply
Authors: David Zakin
Journal: JAMA (1982)

<h3>In Reply.—</h3> Dr Richardson correctly states that we advocate hysterography as the procedure of choice for demonstrating uterine perforation by an IUD. In Dr Richardson's patient, whose IUD string was missing six days after insertion of a Cu-7 IUD, intracavitary exploration did not reveal an IUD, and plain x-ray films (anteroposterior and lateral) showed that it was in the pelvis. At this stage, we would have immediately proceeded to hysterography, which can reliably distinguish between complete perforation, partial perforation, and deep embedding— distinctions that influence the therapeutic approach.<sup>1,2</sup>Sonography cannot distinguish between a normally placed IUD and deep embedding; it can diagnose partial perforation, but cannot give the extent or variety (which is easily determined with hysterography); and it can diagnose complete perforation only when the IUD is close to the uterus. In this particular case, sonography, which was first resorted to, should theoretically have been diagnostic, since the
A MODIFIED DIRECTOR.
Authors: E. R. LARNED
Journal: JAMA (1896)

For the purposes of blunt dissection, no surgical instrument is so universally used as the grooved "director" devised by Professor Kocher of Berne, and yet it does not fully meet all the requirements of the general surgeon. The writer does not claim perfection for this modified instrument, but believes that the alterations from the original have added very largely to its usefulness. These changes consist in having the entire instrument made from one piece of metal (the handle portion being concave on two sides to decrease weight) for it is obvious that a solid instrument will not make as many visits to the repair shop as the one with a soldered hollow handle. The blade has been made longer, more curved and much thinner than the ordinary director to facilitate working<i>around</i>glandular structures, in vascular regions, particularly in operations for the enucleation of tubercular and carcinomatous glands, and in
Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.
Authors: G W Lucier, K G Nelson, R B Everson, T K Wong, R M Philpot, T Tiernan, M Taylor, G I Sunahara
Journal: Environmental Health Perspectives (1987)

Our studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed "Yu-Cheng" in Chinese. Based on data from experimental animal models, we examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. We also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. Our results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6 [derived from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced rabbit lung]. No other cytochrome P-450 isozyme was detected in placental preparations, and the form 6 homolog was found only in placentae from exposed women. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties (Kd and Bmax). The EGF receptor autophosphorylation effect correlated well with the decrease in birthweight observed in offspring of exposed women, suggesting that this biochemical event might provide a good marker of effect for the toxic halogenated aromatics.
Porphyria cutanea tarda and beta-thalassaemia minor
Authors: A G Smith, J B Greig
Journal: BMJ (1980)

had low toxicity and gave an overall response rate of 73%0.In the multicentre study in 153 patients there were no drug-related deaths.We conclude that intracavitary bleomycin is well tolerated and is effective as palliative treatment for malignant effusions, preventing the need for frequent aspiration of accumulated fluid.Because of its lack of haematological toxicity it may be used safely in the already leucopenic patient.
Cheaters never prosper, sometimes
Authors: H. Lorne Carmichael
Journal: Behavioral and Brain Sciences (1995)

Abstract In the Frank (1988) model, a small increase in the number of cheaters will soon be reversed. It is not clear that this prediction holds for sociopathy. There are also many attractive evolutionary models that do not admit a small, stable proportion of cheaters. Hence, without definitive evidence about the character of early human society, we cannot conclude that sociopathy has an evolutionary origin.
Interleukin-6 Signaling in Liver-Parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action
Authors: F. Thomas Wunderlich, Peter Ströhle, A. Christine Könner, Sabine Gruber, Sulay Tovar, Hella S. Brönneke, Lisa Juntti-Berggren, Luo-Sheng Li, Nico van Rooijen, Claude Libert, Per-Olof Berggren, Jens C. Brüning
Journal: Cell Metabolism (2010)
Autonomic Neuropathy in Diabetes Mellitus: A Follow-up Study
Authors: Göran Sundkvist, Bo Lilja
Journal: Diabetes Care (1985)

To evaluate the development of autonomic neuropathy, 23 patients with a moderate (group A) and 18 patients with a long (group B) duration of diabetes and without symptoms of autonomic neuropathy were re-investigated 6 yr after the initial studies. Autonomic nerve function was evaluated from heart reactions to deep breathing (E/I ratio) and to a rapid 90° tilt (acceleration and brake indices). Symptoms of autonomic neuropathy (SAN) developed in 18 patients (nine in each group) who showed a low mean E/I ratio and brake index in both studies. In group A, but not in group B, patients with SAN showed a decrease in the acceleration index and most SAN patients (8/9) in group A had an abnormal acceleration index in the follow-up study. We conclude that in both groups SAN developed rapidly and was preceded by decreases in E/I ratio and brake index.
Abstract 2796: Efficacy and biomarker modulation by AZD1208, a novel, potent and selective pan-Pim kinase inhibitor, in models of acute myeloid leukemia
Authors: Erika Keeton, Kristen McEachern, Marat Alimzhanov, Suping Wang, Yichen Cao, Larry Bao, Sangeetha Palakurthi, Michael Grondine, Yuching Chen, Keith Dillman, Dharmaraj Chinnappan, Minhui Shen, Les Dakin, Xiaolan Zheng, Michelle Lamb, Allan Wu, Huawei Chen, Paul Lyne, Dennis Huszar
Journal: Cancer Research (2012)

Abstract The Pim serine/threonine kinase family is composed of three highly homologous members; Pim-1, Pim-2 and Pim-3, identified by the ability of the prototype member Pim-1 to drive lymphomagenesis in mice. Upregulation of Pim-1 and Pim-2 is observed in leukemias and lymphomas, including AML, NHL and CLL, highlighting the potential of these kinases as therapeutic targets in these indications. Overexpression of Pim-1 or Pim-3 has also been observed in prostate, pancreatic, gastric, bladder and hepatocellular cancers. Pim kinases are downstream effectors of many cytokine and growth factor signaling pathways and are direct transcriptional targets of STAT transcription factors activated by these pathways. Pims can phosphorylate multiple substrates to mediate cell proliferation and survival. Here we describe the activity of AZD1208, an orally available, potent and highly selective Pim inhibitor that effectively inhibits all three isoforms. AZD1208 inhibits the growth of several AML cell lines and sensitivity correlates with the level of Pim-1 expression, STAT5 activation and presence of protein tyrosine kinase mutation. AZD1208 causes cell cycle arrest and apoptosis in MOLM-16 cells in culture. This is accompanied by a dose-dependent reduction in phosphorylation of BAD, 4EBP1 and p70S6K. AZD1208 suppresses the growth of MOLM-16 and KG-1a xenograft tumors in vivo in a dose proportional manner. In addition, AZD1208 leads to potent inhibition of colony growth of primary AML cells from bone marrow aspirates and downregulates phosphorylation of Pim targets. These results underscore the therapeutic potential of Pim kinase inhibition by AZD1208 for the treatment of AML. They also further support investigation of this inhibitor in other hematological and solid tumor malignancies where PIM signaling may play a role in tumorigenesis and survival. 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 2796. doi:1538-7445.AM2012-2796
Comparison of the cost of radiofrequency catheter modification of the atrioventricular node and medical therapy for drug-refractory atrioventricular node reentrant tachycardia
Authors: Steven J. Kalbfleisch, Hugh Calkins, Jonathan J. Langberg, Rafel El-Atassi, Angel Leon, Mark Borganelli, Fred Morady
Journal: Journal of the American College of Cardiology (1992)