tbuckley/cabot-search huggingface dataset:
In Vivo Analysis of Adrenergic Receptor Activity of Dobutamine
Authors: NORMAN W. ROBIE, DONALD O. NUTTER, CARROLL MOODY, JOHN L. MCNAY
Journal: Circulation Research (1974)

Studies were performed in anesthetized dogs to evaluate the cardiac and systemic effects of intravenously administered dobutamine and to determine its direct effects on the renal and femoral vascular beds. The results demonstrated that dobutamine possessed an inotropic efficacy similar to that of isoproterenol and norepinephrine; its chronotropic effect was similar to or greater than that of norepinephrine. In contrast to norepinephrine, dobutamine increased cardiac output and reduced total peripheral resistance with minimal effects on mean aortic pressure. Studies on the denervated hind limb demonstrated that dobutamine stimulated both alpha and beta receptors. The dose of dobutamine which produced a 50% increase in femoral blood flow was 180 times the required dose of isoproterenol and the dose which produced a 50% increase in contractile force was 43 times the required dose of isoproterenol. Studies on the renal vasculature demonstrated that dobutamine caused no dopamine-like renal vasodilator activity and only minor vasodilation mediated by beta receptors. We concluded that dobutamine is more cardioselective than is isoproterenol. The dobutamine-induced decrease in peripheral resistance observed in the whole dog was presumably due to increased myocardial contractility coupled with a greater net effect of beta-adrenergic vasodilation than alpha-adrenergic vasoconstriction. Studies with reserpine-treated dogs showed that all dobutamine-induced effects were due to a direct action on receptors.
Chimeric hepatitis B virus/hepatitis C virus envelope proteins elicit broadly neutralizing antibodies and constitute a potential bivalent prophylactic vaccine
Authors: Elodie Beaumont, Romuald Patient, Christophe Hourioux, Isabelle Dimier-Poisson, Philippe Roingeard
Journal: Hepatology (2012)

The development of a prophylactic vaccine against hepatitis C virus (HCV) has become an important medical priority, because 3-4 million new HCV infections are thought to occur each year worldwide. Hepatitis B virus (HBV) is another major human pathogen, but infections with this virus can be prevented with a safe, efficient vaccine, based on the remarkable ability of the envelope protein (S) of this virus to self-assemble into highly immunogenic subviral particles. Chimeric HBV-HCV envelope proteins in which the N-terminal transmembrane domain of S was replaced with the transmembrane domain of the HCV envelope proteins (E1 or E2) were efficiently coassembled with the wild-type HBV S protein into subviral particles. These chimeric particles presented the full-length E1 and E2 proteins from a genotype 1a virus in an appropriate conformation for formation of the E1-E2 heterodimer. Produced in stably transduced Chinese hamster ovary cells and used to immunize New Zealand rabbits, these particles induced a strong specific antibody (Ab) response against the HCV and HBV envelope proteins in immunized animals. Sera containing anti-E1 or anti-E2 Abs elicited by these particles neutralized infections with HCV pseudoparticles and cell-cultured viruses derived from different heterologous 1a, 1b, 2a, and 3 strains. Moreover, the anti-hepatitis B surface response induced by these chimeric particles was equivalent to the response induced by a commercial HBV vaccine.Our results provide support for approaches based on the development of bivalent HBV-HCV prophylactic vaccine candidates potentially able to prevent initial infection with either of these two hepatotropic viruses.
Adherence and Persistence With Oral Adjuvant Chemotherapy in Older Women With Early-Stage Breast Cancer in CALGB 49907: Adherence Companion Study 60104
Authors: Ann H. Partridge, Laura Archer, Alice B. Kornblith, Julie Gralow, Debjani Grenier, Edith Perez, Antonio C. Wolff, Xiaofei Wang, Helen Kastrissios, Donald Berry, Clifford Hudis, Eric Winer, Hyman Muss
Journal: Journal of Clinical Oncology (2010)

Patient adherence is critical in evaluating the effectiveness of an oral therapy. We sought to measure adherence among women randomly assigned to capecitabine in a preplanned substudy of a multicenter clinical trial.Cancer and Leukemia Group B study CALGB 49907 was a randomly assigned trial comparing standard chemotherapy versus oral chemotherapy with capecitabine in patients age 65 years or older with early-stage breast cancer. We used microelectronic monitoring system (MEMS) caps on participants' capecitabine bottles to record pill bottle openings. Capecitabine was given in two divided daily doses for 14 consecutive days of a 21-day cycle for six cycles. Adherence was calculated as the number of doses taken divided by doses expected, taking into account toxicity-related dosing changes. A participant was defined as adherent if 80% or more of expected doses were recorded by MEMS.Overall, 161 patients were enrolled. Median age was 71 years (range, 65 to 89 years); 124 patients (83%) persisted with capecitabine to completion of planned protocol therapy. Adherence was 78% across all cycles, and adherence did not vary by cycle (P = .32). Twenty-five percent of participants took fewer than 80% of expected doses and were nonadherent. In a logistic regression model, participants with node-negative disease (P = .01) and mastectomy (P = .01) were more likely to be nonadherent. Adherence was not related to age, tumor stage, or hormone receptor status. Adherence was not significantly associated with relapse-free survival or grade 3 or 4 toxicity.Most older women with early-stage breast cancer were adherent to short-term oral chemotherapy in a randomized clinical trial. Age was not associated with adherence.
Fighting tuberculosis: An old disease with new challenges
Authors: Rama P. Tripathi, Neetu Tewari, Namrata Dwivedi, Vinod K. Tiwari
Journal: Medicinal Research Reviews (2004)

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. The mortality and spread of this disease has further been aggravated because of synergy of this disease with HIV. A number of anti-TB drugs are ineffective against this disease because of development of resistance strains. Internationally efforts are being made to develop new anti-tubercular agents. A number of drug targets from cell wall biosynthesis, nucleic acid biosynthesis, and many other biosynthetic pathways are being unraveled throughout the world and are being utilized for drug development. In this review, socioeconomic problems in developing countries, efforts to control this disease in different individuals, the targets (known already and newly discovered), existing anti-tubercular agents including natural products and lead molecules, and the future prospects to develop new anti-TB agents are described. © 2004 Wiley Periodicals, Inc.
Neurobiology of Economic Choice: A Good-Based Model
Authors: Camillo Padoa-Schioppa
Journal: Annual Review of Neuroscience (2011)

Traditionally the object of economic theory and experimental psychology, economic choice recently became a lively research focus in systems neuroscience. Here I summarize the emerging results and propose a unifying model of how economic choice might function at the neural level. Economic choice entails comparing options that vary on multiple dimensions. Hence, while choosing, individuals integrate different determinants into a subjective value; decisions are then made by comparing values. According to the good-based model, the values of different goods are computed independently of one another, which implies transitivity. Values are not learned as such, but rather computed at the time of choice. Most importantly, values are compared within the space of goods, independent of the sensorimotor contingencies of choice. Evidence from neurophysiology, imaging, and lesion studies indicates that abstract representations of value exist in the orbitofrontal and ventromedial prefrontal cortices. The computation and comparison of values may thus take place within these regions.
Highly efficient gene transfer into adult ventricular myocytes by recombinant adenovirus.
Authors: L A Kirshenbaum, W R MacLellan, W Mazur, B A French, M D Schneider
Journal: Journal of Clinical Investigation (1993)

Molecular dissection of mechanisms that govern the differentiated cardiac phenotype has, for cogent technical reasons, largely been undertaken to date in neonatal ventricular myocytes. To circumvent expected limitations of other methods, the present study was initiated to determine whether replication-deficient adenovirus would enable efficient gene transfer to adult cardiac cells in culture. Adult rat ventricular myocytes were infected, 24 h after plating, with adenovirus type 5 containing a cytomegalovirus immediate-early promoter-driven lacZ reporter gene and were assayed for the presence of beta-galactosidase 48 h after infection. The frequency of lacZ+ rod-shaped myocytes was half-maximal at 4 x 10(5) plaque-forming units (PFU) and approached 90% at 1 x 10(8) PFU. Uninfected cells and cells infected with lacZ- virus remained colorless. Beta-galactosidase activity concurred with the proportion of lacZ+ cells and was contingent on the exogenous lacZ gene. At 10(8) PFU/dish, cell number, morphology, and viability each were comparable to uninfected cells. Thus, adult ventricular myocytes are amenable to efficient gene transfer with recombinant adenovirus. The relative uniformity for gene transfer by adenovirus should facilitate tests to determine the impact of putative regulators upon the endogenous genes and gene products of virally modified adult ventricular muscle cells.
Abstract LB-323: Self-reported sleep duration and subsequent risk of colorectal cancer in two large cohorts of women and men
Authors: Xuehong Zhang, Edward Giovannucci, Kana Wu, Xiang Gao, Frank Hu, Shuji Ogino, Eva Schernhammer, Charles Fuchs, Michael Pollak, Walter Willett, Jing Ma
Journal: Cancer Research (2012)

Abstract Background: Short sleep duration was associated with an increased risk of colorectal adenomas in a recent report. To date, no data are available on the relationship between sleep duration and colorectal cancer risk. Method: We prospectively followed 76,368 women aged 40 to 73 years in the Nurses’ Health Study and 28,676 men aged 41 to 79 years in the Health Professionals Follow-up Study who reported their habitual sleep duration in the mid-1980s. We used Cox proportional hazards regression models to estimate multivariable relative risks (MV RRs) and 95% confidence intervals (CIs) adjusting for known risk factors (dietary and non-dietary) for colorectal cancer. Results: A total of 1,925 incident colorectal cancer cases (1,264 in women and 661 in men) were documented during up to 22 years of follow-up. The median of sleep duration was 7 hours in both cohorts and was used as the reference group. In both age-adjusted and the multivariate models, long sleep duration (i.e., at least 9 hours of sleep) was significantly positively associated with risk of colorectal cancer in men (MV RR=1.49; 95%CI: 1.10, 2.03) but not in women (MV RR=1.10; 95%CI: 0.85, 1.43). However, for the same comparison (i.e., at least 9 hours vs. 7 hours of sleep), among overweight (body mass index at least 25 kg/m2) individuals, we found significant positive associations for both men (MV RR=2.66; 95%CI: 1.81, 3.90) and women (MV RR=1.42; 95%CI: 1.01, 1.99). Short sleep duration (i.e., 5 hours or less of sleep) was not associated with colorectal cancer risk in either men (MV RR=0.65; 95%CI: 0.33, 1.28) or women (MV RR=1.14; 95%CI: 0.88, 1.48). Results were essentially unchanged when we excluded cases occurred in the first 4 years of follow-up. In addition, the association was not significantly modified by physical activity, alcohol consumption, endoscopy screening, family history of colorectal cancer, menopausal status, or shift work (women only). Conclusion: These prospective data from two large cohorts suggest that overweight men and women with a sleep duration of 9 or longer hours had a significantly increased risk of developing colorectal cancer when compared to those with 7 hours of sleep, which cannot be explained by known risk factors or reverse causality. The potential mechanisms behind this association deserve further investigation. 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 LB-323. doi:1538-7445.AM2012-LB-323
Murine CD4+ T cell subsets defined.
Authors: K Hayakawa, R R Hardy
Journal: The Journal of Experimental Medicine (1988)

We have used two monoclonal anti-murine T cell autoantibodies (SM3G11 and SM6C10) and multi-color immunofluorescence staining to resolve splenic CD4+ cells into four populations. Two of these populations (Fr. I and Fr. III, 35% and 10% of CD4+ cells) show mutually exclusive expression of these determinants and exhibit distinct functions. Fr. III secretes IL-4, but not IL-2 when activated by Con A, and includes memory T cells responsible for secondary antibody formation. In contrast, Fr. I secretes IL-2 but not IL-4 in response to Con A, and does not contribute to the secondary antibody response. Furthermore, these two fractions exhibit differential accessory cell dependence. Whereas Fr. III responds with B cells (and also non-B cells) as accessory cells in Con A-induced activation, Fr. I requires non-B cells. However, we found that many CD4+ cells (Fr. II, 40% of CD4+ cells) express both determinants and are not distinguishable with regard to lymphokine secretion, accessory cell effect, and memory T cell activity. Curiously, the fraction expressing neither determinant (Fr. IV, 10% of CD4+ cells) is unresponsive to experimental conditions used here. We discuss the possible relationships between these T cell subsets and the implications of differential expression of these determinants.
Opposing time trends of peptic ulcer and reflux disease
Authors: H B El-Serag, A Sonnenberg
Journal: Gut (1998)

Background —Gastritis associated hypochlorhydria may be protective against gastro-oesophageal reflux disease. It was hypothesised that the historic decline in Helicobacter pylori infection resulted in a decline in peptic ulcer and a concomitant rise in reflux disease. Aims —To study the time trends of peptic ulcer and reflux disease. Methods —Hospitalisation rates were analysed using the computerised database of the US Department of Veterans Affairs from 1970 until 1995. Death rates were calculated from the Vital Statistics of the United States. Results —From 1970 to 1995, hospitalisation rates for gastric and duodenal ulcer, as well as gastric cancer fell, while the hospitalisation rates for gastro-oesophageal reflux disease and those for oesophageal adenocarcinoma rose significantly. Similar time trends were observed with respect to the death rates. There were notable ethnic differences. White subjects incurred higher rates of reflux disease and oesophageal adenocarcinoma and lower rates of gastric ulcer or cancer compared with non-whites. Conclusions —The ethnic variations and the opposing time trends of gastroduodenal versus oesophageal disease are consistent with the hypothesis that the declining infection rates of H pylori in the general population have led to a rise in the occurrence of gastro-oesophageal reflux disease and associated oesophageal adenocarcinoma.
Proteomic-Based Detection of Urine Proteins Associated with Acute Renal Allograft Rejection
Authors: Stefan Schaub, David Rush, John Wilkins, Ian W. Gibson, Tracey Weiler, Kevin Sangster, Lindsay Nicolle, Martin Karpinski, John Jeffery, Peter Nickerson
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved by the development of non-invasive markers of rejection that can be measured frequently. This study sought to determine whether such candidate proteins can be detected in urine using mass spectrometry. Four patient groups were rigidly defined on the basis of allograft function, clinical course, and allograft biopsy result: acute clinical rejection group (n = 18), stable transplant group (n = 22), acute tubular necrosis group (n = 5), and recurrent (or de novo) glomerulopathy group (n = 5). Urines collected the day of the allograft biopsy were analyzed by mass spectrometry. As a normal control group, 28 urines from healthy individuals were analyzed the identical manner, as well as 5 urines from non-transplanted patients with lower urinary tract infection. Furthermore, sequential urine analysis was performed in patients in the acute clinical rejection and the stable transplant group. Three prominent peak clusters were found in 17 of 18 patients (94%) with acute rejection episodes, but only in 4 of 22 patients (18%) without clinical and histologic evidence for rejection and in 0 of 28 normal controls (P < 0.001). In addition, the presence or absence of these peak clusters correlated with the clinicopathologic course in most patients. Acute tubular necrosis, glomerulopathies, lower urinary tract infection, and cytomegalovirus viremia were not confounding variables. In conclusion, proteomic technology together with stringent definition of patient groups can detect urine proteins associated with acute renal allograft rejection. Identification of these proteins may prove useful as non-invasive diagnostic markers for rejection and the development of novel therapeutic agents. E-mail: [email protected]
The Radical Cure of Prostatic Obstruction by the Galvano-Cautery
Authors: W. B. Clarke
Journal: BMJ (1892)

JI mo 1321 rated to dryness and exhausted with absolute alcohol.The alcoholic solution on evaporation deposited microscopic acicular crystals.A fragment of the putrid liver, swarming with bacterial life, but in which no characteristic pathogenic forms could be detected, was macerated in water previously sterilised by heat, and some of the macerated fluid was inoculated beneath the skin of the flanks of three guinea-pigs.All died within twenty-four hours.Two of the animals exhibited no par- ticular po8t-nortem appearances.The third had much cedema about the site of inoculation, there was fluid in the peritoneal cavity, the spleen was enlarged and much congested, and the intestineswere emphysematous.The edematousfluid from the site of inoculation, the peritoneal fluid, and the spleen juice all abounded in bacilli, similar in appearance to those of malignant cedema.Some were single rods, but many were prolonged into long jointed threads.No spores were seen.A large, old, grey, wild buck rat was now fed on the re- mainder of the liver-less than half an ounce.It was found dead in eighteen hours.No bacteria were found in the blood nor in the spleen juice, though this organ was congested.It will be noted that the liver was toxic to a rat, and toxic and capable of producing a malignant cedema in the guinea-pig, but that I failed to obtain from it a toxic alkaloid.Lastly, a large, old, grey, wild buck rat was fed on a small piece of the putrid stomach of the deceased.It died in about twenty hours.No bacteria were found either in the blood or the spleen juice of this animal after death.REMARK5S.-Myevidence given at the inquest on the body of the deceased man, before I had experimented on the guinea-pigs, expresses an opinion which my later experiments have confirmed, and was as follows:-" My experiments show that a poison of the class produced by decomposition of animal matter was contained in some of the fish, and not at all, or not in deadly quantity, in other of the fish, and that the same poison was present in the vomit and stomach of the deceased man."That a ptomaine and not the direct action of bacteria was the cause of the death of W. H. seems to me clear from the above experiments.Nevertheless, the facts that there was cedema of the thigh of.the deceased man, and that his liver was capable of producing malignant cedema in a guinea-pig are curious.I incline to the opinion that the ptomaine was generated before the tinning of the sardines.My thanks are due to Surgeon-Captain Weston for his care in supplying me with the history of this most interesting case,'and, above all, to Dr. Washbourn, without whose aid and advice the investigation must have been more incomplete than it still is.
Prevalence of Chronic Obstructive Pulmonary Disease in Korea
Authors: Dong Soon Kim, Young Sam Kim, Ki-Suck Jung, Jung Hyun Chang, Chae-Man Lim, Jae Ho Lee, Soo-Taek Uh, Jae Jeong Shim, Woo Jin Lew
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Although chronic obstructive pulmonary disease is a leading cause of mortality and morbidity worldwide, there are only limited data on its prevalence, especially in Asia.A population-based epidemiologic survey of chronic obstructive pulmonary disease in a representative national sample was conducted using spirometry.A stratified multistage clustered probability design was used to select a nationally representative sample. The survey was performed in conjunction with the second Korean National Health and Nutrition Examination Survey of 9,243 adults over the age of 18 years. The participation rate was 88.8% for questionnaires and 52.1% for spirometry.The prevalence of chronic obstructive pulmonary disease based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (a ratio of FEV1 to FVC of less than 0.7) was 17.2% (men, 25.8%; women, 9.6%) among subjects older than 45 years. Among adults of all ages (age>18 years), the prevalence of airflow obstruction was 7.8% (10.9% in men, 4.9% in women). The majority of these cases were found to be mild in degree, and only a minority of these subjects had received physician diagnosis or treatment. Multivariate analysis revealed that age over 65 years, male sex, smoking more than 20 pack-years, and low income were independent predictors for chronic obstructive pulmonary disease.Seventeen percent of Korean adults over the age of 45 years have mild chronic obstructive pulmonary disease.
Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated
Authors: Hua-Xin Liao, Xi Chen, Supriya Munshaw, Ruijun Zhang, Dawn J. Marshall, Nathan Vandergrift, John F. Whitesides, Xiaozhi Lu, Jae-Sung Yu, Kwan-Ki Hwang, Feng Gao, Martin Markowitz, Sonya L. Heath, Katharine J. Bar, Paul A. Goepfert, David C. Montefiori, George C. Shaw, S. Munir Alam, David M. Margolis, Thomas N. Denny, Scott D. Boyd, Eleanor Marshal, Michael Egholm, Birgitte B. Simen, Bozena Hanczaruk, Andrew Z. Fire, Gerald Voss, Garnett Kelsoe, Georgia D. Tomaras, M. Anthony Moody, Thomas B. Kepler, Barton F. Haynes
Journal: The Journal of Experimental Medicine (2011)

The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non–HIV-1 antigens.