tbuckley/cabot-search huggingface dataset:
Replication priority of hepatitis C virus genotype 2a in a Chinese cohort
Authors: Zhen Yang, Yongxin Yu, Hongzhong Zhang, Guifang Shang, Jialiang Gao, Jian-Dong Jiang, Zonggen Peng
Journal: Acta Pharmaceutica Sinica B (2014)

HCV genotypes have been documented in clinical practice. The aim of this study was to determine the replication priority of different HCV genotypes in a Chinese HCV positive cohort. Serum samples from 491 apparently healthy Chinese blood donors testing positive for HCV antibodies and naive to antiviral drug therapy were tested. Genotyping analysis showed that genotypes 1b and 2a were predominant and accounted for 77.6% of the HCV infections. Among the genotype groups, individuals infected with genotype 2a had an HCV RNA viral load (10(8) copies/mL) about 200-fold (lg, 2.3) greater than those infected with other genotypes (10(4)-10(5) copies/mL) indicating a replication priority of genotype 2a. However, there was no correlation between HCV genotype and antibody response suggesting that the amplification advantage of genotype 2a results from a favorable interaction with the host cellular environment. In conclusion, HCV genotypes 1b and 2a are the predominant genotypes in China and genotype 2a possesses a significant replication priority compared with the other genotypes. This suggests the existence of host cellular factors that may act as drug-targets for entirely clearing HCV infection in the future.
A Phase II Trial of Erlotinib Monotherapy in Pretreated Patients with Advanced Non-small Cell Lung Cancer Who Do Not Possess Active EGFR Mutations: Okayama Lung Cancer Study Group Trial 0705
Authors: Hiroshige Yoshioka, Katsuyuki Hotta, Katsuyuki Kiura, Nagio Takigawa, Hidetoshi Hayashi, Shingo Harita, Shoichi Kuyama, Yoshihiko Segawa, Haruhito Kamei, Shigeki Umemura, Akihiro Bessho, Masahiro Tabata, Mitsune Tanimoto
Journal: Journal of Thoracic Oncology (2010)
Choice between long- and short-term interests: Beyond self-control
Authors: Leonard Green, Joel Myerson
Journal: Behavioral and Brain Sciences (1995)

Abstract In the real world, there are choices between large, delayed, punctate rewards and small, more immediate rewards as well as choices between patterns and acts. A common element in these situations is the choice between long- and short-term interests. Key issues for future research appear to be how acts are restructured into larger patterns of behavior, and whether, as Rachlin implies, pattern perception is the cause of pattern generation.
Book: Oxford Handbook of Patients' Welfare: A Doctor's Guide to Benefits and Services
Authors: R. Neal
Journal: BMJ (1999)

Adam Sandell Oxford University Press, £18.95, pp 283 ISBN 0 19 262957 3 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> The welfare of patients is at centre of medical care, either at the level of delivering “technical” welfare (removing a gall bladder or prescribing antibiotics to an ill child with otitis media) or delivering “social” welfare (non-medical interventions to improve health). Such social interventions include pastoral and spiritual support and providing practical and financial advice to improve quality of life. The balance between the provision … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Tamoxifen Flare in Advanced Breast Cancer
Authors: David Plotkin
Journal: JAMA (1978)

The antiestrogen tamoxifen citrate is an effective antitumor agent in postmenopausal women with advanced breast cancer. The drug has produced relatively few and generally mild side effects. However, a not uncommon clinical phenomenon that may falsely suggest premature discontinuation of tamoxifen therapy has become evident to us and has not yet been sufficiently emphasized in the literature. We have designated this phenomenon as the tamoxifen flare. It consists of transient, at times severe, increase in pain with an apparent worsening of the patient's clinical status occurring within the first few weeks of therapy. In each of six patients experiencing this flare (45 patients treated) pain subsided despite continuation of tamoxifen therapy, followed by a partial remission lasting from six to 20 months. (<i>JAMA</i>240:2644-2646, 1978)
THE DIAGNOSIS AND TREATMENT OF PERFORATION IN TYPHOID FEVER.WITH A REPORT OF 19 CASES, OF WHICH 16 WERE OPERATED ON, WITH FIVE RECOVERIES.
Authors: MORRIS MANGES
Journal: JAMA (1905)

The diagnosis and treatment of acute appendicitis are now so clearly defined and so generally recognized that it hardly seems credible that about twenty-five years ago bitter controversies were being waged in New York City as to the propriety of the use of the aspirating needle in the diagnosis of this condition, and an occasional recovery after the opening of an appendicular abscess attracted great attention. It was at about this time, in 1884, that Leyden first made the suggestion that perforation occurring during the course of typhoid fever should be treated surgically. Contrast the fact that thousands of cases of appendicitis are now successfully operated on annually and that a paltry 362 cases constitute the whole literature of surgically treated typhoid perforation! And this for a condition which, according to the well-known statistics of Taylor, costs from 20,000 to 25,000 lives yearly in the United States alone.
The analogy between dreams and the ancient art of memory is tempting but superficial
Authors: Nikolai Axmacher, Juergen Fell
Journal: Behavioral and Brain Sciences (2013)

Although the analogy between dreams and ancient mnemotechniques is tempting because they share several phenomenological characteristics, this analogy is superficial at a closer look. Unlike mneomotechnically encoded material, rapid eye movement (REM) dreams are inherently difficult to remember, do not usually allow conscious subsequent retrieval of all interconnected elements, and have been found to support subsequent episodic memory in only rare cases.
873. Adenovirus Polypeptide IIIa as a Novel Locale for Incorporation of Heterologous Peptides
Authors: Joel N. Glasgow, Elena Kashentseva, Igor P. Dmitriev, David T. Curiel
Journal: Molecular Therapy (2005)

Top of pageAbstract
The utility of the present generation of recombinant adenovirus (Ad) vectors for gene therapy applications could potentially be improved by restricting broad native viral tropism to selected cell types. In order to achieve cell-specific targeting of Ad vectors, we have proposed modification of viral tropism via genetic engineering of the viral coat proteins to include targeting ligands. To this end, major Ad capsid proteins fiber, hexon, penton and the minor capsid protein polypeptide IX (pIX) have been exploited as platforms for the presentation of ligand peptides. While each of these capsid locales may be of utility, additional capsid locales for the presentation of heterologous peptides should be investigated. The adenovirus capsid protein pIIIa is a 570 amino acid protein present in the virion as a 63.5 kDa monomer. Structural studies indicate that sixty copies of pIIIa are present in the Ad5 virion, with two pIIIa monomers positioned along each of the thirty icosahedral edges. Further, cryo-electron microscopy studies indicate that the bulk of pIIIa is localized to the outer surface of the virion. Based on these considerations, we hypothesized that the minor capsid protein pIIIa could be exploited as a novel locale for ligand incorporation. In this study, we engineered recombinant Ad vector genomes encoding pIIIa modified to incorporate a 6-Histidine tag or FLAG octapeptide/6-Histidine at the N-terminus. Both pIIIa Ad variants were rescued, indicating that the presence of these non-native pIIIa proteins does not significantly disturb viral replication and/or assembly. Further, by using the relevant specific antibodies, we have confirmed that FLAG- and 6His-containing pIIIa chimeric capsomers are incorporated into virions, and are accessible for binding. These findings suggest that pIIIa may possess properties consistent with its employment in Ad capsid modification strategies and may be a promising locale for incorporation of targeting moieties.
Effects of volume loading during experimental acute pulmonary embolism.
Authors: I Belenkie, R Dani, E R Smith, J V Tyberg
Journal: Circulation (1989)

Volume loading is used to treat hemodynamically compromised patients with acute pulmonary embolism despite data to suggest that volume loading after embolism might cause a leftward shift of the ventricular septum with a subsequent decrease in left ventricular (LV) end-diastolic volume and stroke work. We studied 10 closed-chest, anesthetized, and ventilated dogs to assess the effects of volume loading after pulmonary embolism caused by autologous clot. LV, right ventricular, and right atrial pressures as well as LV anteroposterior, septum-to-right ventricular, and septum-to-LV free wall diameters (sonomicrometry) were measured. Pericardial pressure was measured with flat, liquid-containing balloons. The effects of volume loading were assessed before embolism, after one episode of embolization, and after repeated embolizations. The LV area index (as a reflection of LV volume) increased during volume loading before embolism (2,870 +/- 430 to 3,080 +/- 520 mm2; p less than 0.05), did not change significantly during infusion of fluid after one embolization (2,850 +/- 470 to 2,860 +/- 500 mm2; p = NS), and decreased significantly during volume expansion after repeated embolizations (2,760 +/- 440 to 2,660 +/- 420 mm2; p less than 0.01). An index of LV stroke work increased (188 +/- 85 to 260 +/- 101 mm Hg x mm2; p less than 0.05), did not change significantly (188 +/- 39 to 203 +/- 52 mm Hg x mm2; p = NS), and decreased markedly (133 +/- 64 to 45 +/- 27 mm Hg x mm2; p less than 0.001) before embolism, after one embolization, and after repeated embolizations, respectively. The decrease in LV area index during volume loading after repeated embolizations was associated with an increase in septum-to-right ventricular free wall diameter (31 +/- 8 to 34 +/- 8 mm; p = 0.001) and a decrease in the septum-to-LV free wall diameter (44 +/- 5 to 42 +/- 5 mm; p less than 0.001), whereas the LV anteroposterior diameter did not change (62 +/- 5 to 63 +/- 5 mm; p = NS). This is compatible with a leftward septal shift being partially responsible for the decrease in LV end-diastolic volume; such a shift would be expected with the observed decrease in transseptal end-diastolic pressure gradient (-3 +/- 2 to -5 +/- 2 mm Hg; p = 0.001). In addition, after repeated embolizations, LV transmural pressure decreased in response to the volume load reflecting a marked increase in pericardial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)
GW25-e3129 β1-Adrenergic receptor-mediated HO-1/HMGB1 axis via PI3K and p38 MAPK attenuates rat myocardial ischemia/reperfusion injury in vivo
Authors: Wang Jichun, Hu Xiaorong, Xie Jing, Zhou Xiaoya, Jiang Hong
Journal: Journal of the American College of Cardiology (2014)
Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-γ and IL-4
Authors: Michael B. Soyka, Paulina Wawrzyniak, Thomas Eiwegger, David Holzmann, Angela Treis, Kerstin Wanke, Jeannette I. Kast, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2012)
Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data
Authors: Hon-Chung Fung, Sonja Scholz, Mar Matarin, Javier Simón-Sánchez, Dena Hernandez, Angela Britton, J Raphael Gibbs, Carl Langefeld, Matt L Stiegert, Jennifer Schymick, Michael S Okun, Ronald J Mandel, Hubert H Fernandez, Kelly D Foote, Ramón L Rodríguez, Elizabeth Peckham, Fabienne Wavrant De Vrieze, Katrina Gwinn-Hardy, John A Hardy, Andrew Singleton
Journal: The Lancet Neurology (2006)
Dimensions of Blood Vessels from Distributing Artery to Collecting Vein
Authors: MARY P. WIEDEMAN
Journal: Circulation Research (1963)

Measurements of lengths, diameters, and numbers of post-capillary vessels were made in the bat's wing. The cross-sectional area and capacity in the various portions of the vascular bed were calculated. The greatest total cross-sectional area in the entire vascular bed was found in the venules, a result not in agreement with similar reports made by others using measurements from vessels in fixed preparations. This discrepancy probably results from disagreement regarding the diameter of capillary vessels. Calculations to determine the per cent of total volume in each portion of the vascular bed showed that the venous system accounts for as much as 80% of the total vascular volume.
Who would want to be medicine's sacrificial lamb?
Authors: J. Sheather
Journal: BMJ (2009)

Audiences can be fickle things. Recently I clambered down from my ivory tower and emerged, blinking, on to a brilliantly lit podium at the Cheltenham science festival. The theme of the evening was “Playing God—risk in surgery.” I was on a panel with two surgeons, but my job was to do the ethics. I figured that the live issue would be about balancing paternalism and autonomy. Was there a limit to the amount of risk a patient could be asked to take on? Could illness and the possibility of death be coercive? Could an ambitious surgeon, keen to make a name, lead the desperate into taking impossible and mutilating risks?

How rose tinted must be the windows of the ivory tower. I could not have been more wrong. A charming cardiac surgeon took us on a walk down memory lane, a long, long walk back to the good old, bad old days, the days before the scandals at Alder Hey and Bristol Royal Infirmary had …
Bruton Tyrosine Kinase Is a Therapeutic Target in Stem-like Cells from Multiple Myeloma
Authors: Ye Yang, Jumei Shi, Zhimin Gu, Mohamed E. Salama, Satyabrata Das, Erik Wendlandt, Hongwei Xu, Junwei Huang, Yi Tao, Mu Hao, Reinaldo Franqui, Dana Levasseur, Siegfried Janz, Guido Tricot, Fenghuang Zhan
Journal: Cancer Research (2015)

Ibrutinib (Imbruvica), a small-drug inhibitor of Bruton tyrosine kinase (BTK), is currently undergoing clinical testing in patients with multiple myeloma, yet important questions on the role of BTK in myeloma biology and treatment are outstanding. Using flow-sorted side population cells from human myeloma cell lines and multiple myeloma primary samples as surrogate for the elusive multiple myeloma stem cell, we found that elevated expression of BTK in myeloma cells leads to AKT/WNT/β-catenin-dependent upregulation of key stemness genes (OCT4, SOX2, NANOG, and MYC) and enhanced self-renewal. Enforced transgenic expression of BTK in myeloma cells increased features of cancer stemness, including clonogenicity and resistance to widely used myeloma drugs, whereas inducible knockdown of BTK abolished them. Furthermore, overexpression of BTK in myeloma cells promoted tumor growth in laboratory mice and rendered side population-derived tumors that contained high levels of BTK more sensitive to the selective, second-generation BTK inhibitor, CGI1746, than side population-derived tumors that harbored low levels of BTK. Taken together, these findings implicate BTK as a positive regulator of myeloma stemness and provide additional support for the clinical testing of BTK-targeted therapies in patients with myeloma.
Predictors of early morbidity and mortality after thrombolytic therapy of acute myocardial infarction. Analyses of patient subgroups in the Thrombolysis in Myocardial Infarction (TIMI) trial, phase II.
Authors: H S Mueller, L S Cohen, E Braunwald, S Forman, F Feit, A Ross, M Schweiger, H Cabin, R Davison, D Miller
Journal: Circulation (1992)

BACKGROUND Thrombolysis has altered treatment of acute myocardial infarction (AMI). Therefore, reevaluation of predictors of outcome and treatment strategies is appropriate. METHODS AND RESULTS Clinical variables collected prospectively for the 3,339 patients of the Thrombolysis in Myocardial Infarction II study were analyzed retrospectively to identify predictors of clinical events at 42 days and earlier and to identify subgroups in which an invasive or conservative strategy might be superior. Pulmonary edema/cardiogenic shock presented as the strongest independent correlate with death (relative risk, 6.0). In two subgroups, mortality differed between the invasive and conservative strategies: 1) Patients with versus without prior AMI had a higher mortality in the conservative strategy (11.5% versus 3.5%, p less than 0.001); in the invasive strategy, the mortality rates were similar (6.0% and 5.1%). 2) Patients with diabetes mellitus and no prior AMI had a higher mortality in the invasive than in the conservative strategy (14.8% versus 4.2%, p less than 0.001). Reinfarction was not independently correlated with baseline characteristics except with history of angina (relative risk, 1.9). Mortality was lower in current smokers and ex-smokers versus never-smokers (3.6% and 4.8% versus 8.0%, p less than 0.001). Current smokers had a lower risk profile (p less than 0.001), including age, pulmonary edema/cardiogenic shock, history of hypertension, and diabetes. The rate of reinfarction was lower in current smokers versus ex-smokers and never-smokers (4.6% versus 8.3% and 8.8%, p less than 0.001). "Not current smoker" was an independent correlate with reinfarction (relative risk, 1.9). The coronary anatomy did not differ among the current smokers, ex-smokers, and never-smokers. CONCLUSIONS The strong independent correlation of pulmonary edema/cardiogenic shock with death suggests that thrombolysis is not sufficient to improve survival in these patients. The higher mortality in patients with versus without prior AMI in the conservative strategy suggests that early catheterization and revascularization of these patients might be beneficial. Conversely, the higher mortality in diabetes without prior AMI in the invasive than in the conservative strategy suggests that early aggressive management might not be suitable in this subgroup except for clinical indications. Reinfarction was not predictable by clinical variables except by history of angina. The finding that "not current smoker" was an independent correlate with reinfarction was unexpected.
Viral dynamics of hepatitis B virus DNA in human immunodeficiency virus-1-hepatitis B virus coinfected individuals: Similar effectiveness of lamivudine, tenofovir, or combination therapy
Authors: Sharon R. Lewin, Ruy M. Ribeiro, Anchalee Avihingsanon, Scott Bowden, Gail Matthews, Pip Marks, Stephen A. Locarnini, Kiat Ruxrungtham, Alan S. Perelson, Gregory J. Dore
Journal: Hepatology (2008)

Abstract Following treatment of hepatitis B virus (HBV) infection with nucleos(t)ide reverse transcriptase inhibitors (NRTIs), there is a biphasic clearance of HBV, similar to that seen following treatment of human immunodeficiency virus-1 (HIV-1) and hepatitis C virus. Little is known about the impact of combination NRTIs and HIV-1 coinfection on HBV viral kinetic parameters following the initiation of HBV-active highly active antiretroviral therapy (HAART). HIV-1–HBV coinfected patients (n = 21) were enrolled in a viral kinetics substudy of the Tenofovir in HIV-1–HBV Coinfection study (TICO). TICO was a randomized (1:1:1) trial of tenofovir disoproxil fumarate (TDF, 300 mg) versus lamivudine (LMV, 300 mg) versus TDF/LMV within an efavirenz based HAART regimen initiated in HIV-1-HBV coinfected antiretroviral naïve individuals in Thailand. HBV DNA was measured frequently over the first 56 days. To fit the viral load data, we used a model of HBV kinetics that allows the estimation of treatment effectiveness, viral clearance and infected cell loss. We observed a biphasic decline in HBV DNA in almost all patients. We did not observe any significant differences in HBV viral dynamic parameters between the three treatments groups. Overall, median (interquartile range) HBV treatment effectiveness was 98% (95%-99%), median HBV virion half-life was 1.2 days (0.5-1.4 days), and median infected cell half-life was 7.9 days (6.3-11.0 days). When we compared hepatitis B e antigen (HBeAg)-positive and HBeAg-negative individuals, we found a significantly longer infected cell half-life in HBeAg-positive individuals (6.2 versus 9.0 days, P = 0.02). Conclusion: HBV viral dynamic parameters are similar following anti-HBV NRTI monotherapy and dual combination therapy in the setting of HIV-1–HBV coinfection. HIV-1 coinfection has minimal effect on HBV viral dynamics, even in the setting of advanced HIV-1–related immunosuppression. (Hepatology 2009.)
Hepatic and extrahepatic glucuronidation of lorazepam in the dog
Authors: John F. Gerkens, Paul V. Desmond, Steven Schenker, Robert A. Branch
Journal: Hepatology (1981)

The pharmacokinetic disposition of lorazepam was investigated in sham-operated aneshetized dogs, dogs with hepatic devascularization, and dogs with total splanchnic devascularization following i.v. administration of 0.3 mg per kg of the drug. In sham-operated dogs, lorazepam distribution was extensive (100 +/- 15.2 liters) and clearance approximately expected liver blood flow (971 +/- 91 ml per min). Lorazepam glucuronide levels in plasma rose rapidly in the first hour and reached a plateau by 5 hr. Urinary recovery of the conjugate in 5 hr was 45% of administered dose. Hepatic devascularization resulted in 39% reduction in distribution volume, and 89% reduction in clearance; however, there was still 105 +/- 88 ml per min of extrahepatic lorazepam clearance. Five-hour urinary recovery of conjugate decreased by 80%. Total splanchnic devascularization resulted in 37% further reduction in extrahepatic clearance, almost complete inhibition of urinary recovery of conjugate, and further reduction in the volume of distribution. It is concluded that the liver is the major site for lorazepam metabolism in dogs; however, appreciable extrahepatic metabolism occurs, partly in nonhepatic components of the splanchnic organs which act as a reservoir during drug distribution.
STUDIES ON THE MUCOPROTEINS OF HUMAN PLASMA. I. DETERMINATION AND ISOLATION 1
Authors: Richard J. Winzler, Arthur W. Devor, John W. Mehl, Irene M. Smyth
Journal: Journal of Clinical Investigation (1948)

The presence in plasma of protein-like materials with properties of polypeptides or proteoses has been demonstrated repeatedly, but little has been done toward the characterization of these materials.The concentration of such materials in plasma rises markedly in patients with cancer or with cer- tain other diseases, but here again little is known of the source or significance of the increased levels.The relation of these protein-like materials to the glycoproteins and mucoproteins of plasma is like- wise in a state of considerable confusion.The present series of experiments has grown out of three distinct avenues of attack (a) the dem- onstration, polarographically, of high molecular weight compounds containing cystine in sulfosali- cylic acid filtrates of serum (1 to 6), (b) the demonstration of polypeptide-like substances in serum deproteinated with trichloracetic acid (7 to 10), and (c) the demonstration of a carbohydrate- rich protein, seromucoid, present in filtrates of serum deproteinated by heat (11 to 14).It ap- pears very likely that these materials are identical, and for reasons that will be developed in this paper, the materials will be referred to as muco- proteins.Winzler and Burk (6) isolated the non-dialyz- able material from sulfosalicylic acid filtrates of rat blood, and compared the properties and occur- rence of this material with the older studies of plasma polypeptides.They concluded that the isolated product was identical with the substances