tbuckley/cabot-search huggingface dataset:
Studies on the role of angiotensin in experimental renovascular hypertension: an immunologic approach
Authors: A. R. Christlieb, T. U. L. Biber, R. B. Hickler
Journal: Journal of Clinical Investigation (1969)

The role of angiotensin in three forms of experimental hypertension was assessed in rats. First, the acute blood pressure response to injected angiotensin amide and angiotensin acid was determined. Rats made hypertensive with deoxycorticosterone and saline showed exaggerated responses; rats made hypertensive by clipping one renal artery showed depressed responses; and rats made hypertensive by clipping one renal artery and contralateral nephrectomy showed normal responsivity to angiotensin amide but depressed responsivity to angiotensin acid. These findings suggested that different mechanisms may be involved in the three types of hypertension studied. To assess the role of angiotensin in these hypertensive rats the blood pressure response, the presence of antibodies determined by radioimmune techniques, and the degree of refractoriness to injected angiotensin after immunization with angiotensin were studied. None of six rats made hypertensive by deoxycorticosterone and saline, and none of five mock immunized rats with renal hypertension of both types had a fall in blood pressure. By contrast, of the 20 rats with both types of renal hypertension in which antibody determinations were made, 11 had developed a significant antibody titer, of which seven showed a significant reduction in blood pressure at the time of antibody determination, and three of the remaining four had a significant blood pressure reduction earlier in their course. None of the nine renal hypertensive rats without demonstrable antibodies had a reduced blood pressure at the time of antibody determination, and only one had an earlier reduction in blood pressure. The renal hypertensive rats were all refractory to injected angiotensin after immunization. These results suggest a primary role for angiotensin in both forms of renal hypertension.
Evaluating health promotion is complex
Authors: V. Speller, A. Learmonth, D. Harrison
Journal: BMJ (1998)

EDITOR—The authors responding to our article on the search for evidence of effective health promotion fail to understand the complexity of evaluating health promotion.1 Britton et al acknowledge that health promotion attempts to intervene at a community or national level, but they contradict this by stating that “most health promotion interventions involve individual behaviour change.” This is true of most health promotion research because behavioural interventions are conducive to experimental evaluation, unlike health goals of organisational and environmental change.

We stand by our argument that …
Abstract 3605: Effects of antibody-mediated EGF-receptor inhibition on ERK 1/2 isoform phosphorylation in organoid cultures
Authors: Florian T. Unger, Cordula Rosenbrock, Jana Krueger, Janina Schaller, Birgit Rabe, Hartmut Juhl, Kerstin A. David
Journal: Cancer Research (2012)

Abstract Inhibition of the EGF-receptor activity has been widely integrated into clinical practice for different tumor entities, e.g. non small lung cancer and colorectal cancer. Besides the application of tyrosine kinase inhibitors, anti-EGF-receptor treatment is mainly based on the application of therapeutic antibodies. As a standard procedure, patients are tested for KRAS mutation and only those without mutation are selected for anti-EGF-receptor therapy. Although KRAS testing is used to guide colorectal cancer treatment, clear heterogeneity in responses to treatment has been observed. The molecular mechanisms responsible for this heterogenity are still not fully understood, In the present study, we used a preclinical model based on tumor tissue slices for a more detailed evaluation of antibody-mediated EGF-receptor inhibition. In previous experiments, the diffusion of antibodies into organoid cultures and the detection of their functional effects had been successfully shown. Tumor tissue slices from five colorectal cancer patients have been treated with an anti-EGF-receptor antibody for 48 hours. Using immunohistochemical staining, one patient showed a strong expression of the EGF-receptor, one was weak positive and three displayed a moderate staining. As readout of treatment effects, the expression and phosphorylation levels of selected key proteins from two EGF-receptor downstream pathways, the MAPK-pathway and Akt-pathway, were measured using the multiplex technology platform from Meso Scale Discovery. For a more detailed view, we have integrated the NanoPro technology in our pathway analysis approach. This new method enables the identification of distinct isoform phosphorylations and thus is able to display the complex regulation of phosphorylation patterns in detail. By using both methods, we observed a dose-dependent regulation of total- and phospho-ERK in the organoid cultures after anti-EGF-receptor treatment. Deeper analysis using the NanoPro technology showed that the regulation of isoform phosphorylation patterns of ERK1/2 differed among patients, representing the heterogeneity of individual responses among patients. In summary, the combination of the organoid drug testing platform and the NanoPro technology can potentially be useful to identify predictive phosphorylation patterns of tumor cells within their natural tumor microenvironment. This may facilitate the discovery of predictive biomarker for the response to anti-EGF-receptor treatment and further improve personalized medicine. 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 3605. doi:1538-7445.AM2012-3605
Incidence of trauma related stress fractures and shin splints in male and female army recruits: retrospective case study
Authors: M A Macleod, A S Houston, L Sanders, C Anagnostopoulos
Journal: BMJ (1999)

The Ministry of Defence's equal opportunities policy, which was introduced in 1993, means that female recruits to army training regiments have been exposed to the same rigorous, physically demanding exercise as men.We noticed a fourfold increase in referrals between 1994 and 1996 and decided to investigate whether this reflected increased referral of women.
High-Tech Medicine and Rising Health Care Costs
Authors: Eli Ginzberg
Journal: JAMA (1990)

SINCE the early 1970s the United States has pursued multiple strategies aimed at moderating the increases in its annual health care expenditures. In the search for causes and cures of health care inflation, high-tech medicine (HTM) is identified increasingly as the major culprit responsible for our steeply rising health care costs. To illuminate the issue, this article offers an operational definition of the term HTM, examines the supporting arguments for the claim that HTM is the principal propellant of escalating health care costs and that it is often counterproductive, reviews the role of public policy in speeding the growth of HTM, and concludes with some forecasts about the probable impact of HTM on future US health care costs. <i>High-tech medicine</i>may be defined simply and comprehensively as the sum of all the advances in medical knowledge and technique that have been translated into improved diagnostic, therapeutic, and rehabilitative procedures during
Michelangelo: A Psychoanalytic Study of His Life and Images
Authors: George H. Pollock
Journal: JAMA (1985)

Admirers of Michelangelo are familiar with one or several of his artistic masterpieces—be they the Sistine Chapel ceiling, the Pietas, the David statue, the Moses, or many other of his numerous creations. Now Robert S. Liebert, MD, has given us his very creative biography of Michelangelo, which is of the highest scholarship and of great aesthetic satisfaction. The parallel creativity of the biographer and the subject of biography seem to have a significant relationship with each other, although a biographer's creativity is different from that of the artistic creator. The biographer is more like a scientific researcher—he has his hypotheses, he seeks to test these with data, he reaches tentative conclusions that can be overturned by new facts, he can at times try to disprove his own hypotheses, and he presents his evidence clearly and unambiguously. Alternative explanations or hypotheses can be considered by others, and they in turn must
Re: Georgios Gakis, Stephen A. Boorjian, Alberto Briganti, et al. The Role of Radical Prostatectomy and Lymph Node Dissection in Lymph Node–Positive Prostate Cancer: A Systematic Review of the Literature. Eur Urol 2014;66:191–9
Authors: Francesco Montorsi, Giorgio Gandaglia
Journal: European Urology (2014)
Abstract 3212: Development of a chemiluminescence-based single telomere length analysis (STELA) method
Authors: Christopher M. Heaphy, Michael C. Haffner, Alan K. Meeker
Journal: Cancer Research (2010)

Abstract Carcinogenesis is a multistep process characterized by the accumulation of genetic alterations that drive the transformation of normal cells to malignant cells. Telomeres are specialized nucleoprotein structures that function to protect and stabilize the ends of eukaryotic chromosomes by preventing chromosome fusions, masking double strand DNA break damage signals and preventing exonucleolytic chromosomal degradation. It is well established that telomere shortening is present in precursor and invasive stages of many carcinomas. Additionally, numerous investigations have demonstrated that altered telomere length predisposes cells to possess the properties necessary for metastasis formation, and therefore represents a predictor of clinical outcome. However, most of these studies have used assays that measure the average telomere length of all the cells in a particular population. To circumvent this problem, Baird et al. (Nature Genetics, 2003) previously described a PCR-based single telomere length analysis (STELA) method that could accurately measure the full spectrum of telomere lengths from a specific chromosomal arm. Although this method represents a substantial improvement over existing methods, the assay requires the use of radioactive material. Here, we describe a modification of the STELA assay which uses chemiluminescence instead of radioisotopes for product visualization, while maintaining the overall sensitivity of the detection of a wide range of telomere lengths. This new methodology has tremendous potential to illuminate the mechanisms that support the initiation of cancer and may provide an avenue for investigators to address the full extent and significance of telomere shortening in the tumorigenic process at the single chromosome level. The modified assay described here will allow for more widespread use of this technique among cancer researchers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3212.
Ezetimibe decreases SREBP-1c expression in liver and reverses hepatic insulin resistance in mice fed a high-fat diet
Authors: Tomonori Muraoka, Kazutaka Aoki, Tomoyuki Iwasaki, Kazuaki Shinoda, Akinobu Nakamura, Hiroyuki Aburatani, Shuuichi Mori, Kumpei Tokuyama, Naoto Kubota, Takashi Kadowaki, Yasuo Terauchi
Journal: Metabolism (2010)
Constitutive activation of distinct BCR-signaling pathways in a subset of CLL patients: a molecular signature of anergy
Authors: Marta Muzio, Benedetta Apollonio, Cristina Scielzo, Michela Frenquelli, Irene Vandoni, Vassiliki Boussiotis, Federico Caligaris-Cappio, Paolo Ghia
Journal: Blood (2008)
Primary Venous Thromboembolism and Cancer Screening
Authors: H. Büller, J. Wouter ten Cate
Journal: New England Journal of Medicine (1998)

For more than a century we have known that deep venous thrombosis or pulmonary embolism may be the presenting feature of an occult cancer. The association between venous thromboembolism and cancer raises three questions: What is the mechanism, how strong is the association, and what are the implications for patient care?The mechanisms of cancer-induced venous thrombosis have been widely studied, mainly in patients with overt cancers. These mechanisms include invasion of cancer cells into the vessel wall, compression of the vasculature by a tumor, and hypercoagulability induced by the cancer. Studies of patients with solid tumors or leukemia using . . .
PHYSIOLOGICAL ONTOGENY
Authors: Alfred E. Cohn, Henry A. Murray
Journal: The Journal of Experimental Medicine (1925)

1. Observations on tissue cultures of heart muscle from chicken embryos indicate that in general the growth rate of the individual cells decreases with age. The negative acceleration of growth is greatest at the beginning of life as in the intact embryo. 2. The latent period before growth commences increases with the age of the implanted tissue, but in a different fashion. The acceleration of the latent period is greatest near the end of the incubation period, thus demonstrating that the factors determining the initiation of growth and those determining the extent of growth are not similar.
The aplastic anemia‐paroxysmal nocturnal hemoglobinuria syndrome
Authors: Marcel E. Conrad, James C. Barton
Journal: American Journal of Hematology (1979)

Abstract Occasionally it is difficult to differentiate paroxysmal nocturnal hemoglobinuria (PNH) from idiopathic aplastic anemia in patients who present with pancytopenia and an aplastic bone marrow. Patients with PNH may not have an abnormal acid hemolysis test, and patients with aplastic anemia may present with evidence of abnormal sucrose lysis, acid hemolysis, and antibody‐mediated complement hemolysis. Demonstration of a population of red blood cells which are highly susceptible to antibody‐mediated complement lysis makes a diagnosis of PNH probable. Donor red blood cell survival studies, which distinguish intracorpuscular from extracorpuscular hemolytic disorders, permit differentiation of the two disorders.
Glucose-Insulin-Potassium Use in Acute Myocardial Infarction
Authors: Tsung O. Cheng
Journal: Circulation (1999)

As my mentor Dr William Dock said, medical practice is like a pendulum: it swings back and forth every 20 to 30 years.Sodi-Pallares et al 1 in 1962 introduced the glucose-insulinpotassium infusion (GIK) for treatment of acute myocardial infarction.It was also called the "polarizing solution," 2 but little did they know that this solution indeed polarized the cardiologists at that time to "believers" and "nonbelievers."Soon the GIK treatment for acute myocardial infarction fell into disrepute due to doubts and conflicting data about its efficacy; its use was subsequently abandoned.Now Diaz et al 3 on behalf of the ECLA (Estudios Cardiolo ´gicos Latinoame ´rica) Collaborative Group were able to show a dramatic reduction of death rate of acute myocardial infarction from 11.5% in the control group to 6.7% in patients treated with GIK.This is the largest reduction of mortality by any intervention that has been tried. 4he results of the GIK study by the ECLA group are most exciting and have serious clinical implications.The GIK treatment costs less than $50 5 compared with over $10 000 for the current vogue of either thrombolytic treatment or catheter inter-ventional therapy for acute myocardial infarction.In this era of managed health care, the economic impact will be tremendous.
Antiphospholipid antibodies, systemic lupus erythematosus, and non-traumatic metatarsal fractures
Authors: S Sangle
Journal: Annals of the Rheumatic Diseases (2004)

Stress fractures are common in military recruits and athletes and are thought to be secondary to stress and overuse. Less often they are associated with metabolic disorders such as osteoporosis, hypophosphataemia, and diabetes mellitus.Analysis of 19 patients with systemic lupus erythematosus and antiphospholipid antibodies presenting consecutively with foot pain. All had metatarsal fractures (six bilateral) without any obvious history of trauma.13 of the 19 patients had antiphospholipid syndrome. Among the whole group, 13 had normal bone mineral density, one had osteopenia, and five others had osteoporosis as defined by WHO criteria; 10 had received steroids, mostly in low dosage; 13 were receiving warfarin. There was no evidence that a metabolic bone abnormality was a unifying factor in the pathogenesis.Atraumatic metatarsal stress fractures may occur in SLE, particularly in association with the antiphospholipid syndrome. The pathogenesis of these fractures remains uncertain but microinfarcts in the metatarsal bones are a possible cause.
Cytomegalovirus causes a latent infection in undifferentiated cells and is activated by induction of cell differentiation
Authors: FJ Dutko, MBA Oldstone
Journal: The Journal of Experimental Medicine (1981)

Murine cytomegalovirus (MCMV) does not productively infect OTT6050AF1 BrdU, F9, or PCC4 undifferentiated murine teratocarcinoma cell lines, as shown by immunofluorescence assays for viral antigens and by plaque assays for infectious virus. However, these cells were infected by a variety of other viruses. MCMV does productively infect PYS2 and OTT F12 differentiated murine teratocarcinoma cell lines. The replication of MCMV in the pluripotent PCC4 cell line was examined in detail. Undifferentiated PCC4 cells could be differentiated when propagated in the presence of dimethylacetamide, as judged by changes in the expression of H-2 antigens on the cell surface. Several viruses, including lymphocytic choriomeningitis virus, herpes simplex virus type 1, and vesicular stomatitis virus, replicated to a similar extent in differentiated and undifferentiated PCC4 cells. MCMV did productively infect differentiated PCC4 cells. In contrast, MCMV did not produce infectious virus, viral antigens, or substantial viral RNA in undifferentiated PCC4 cells. The molecular block of MCMV replication occurred at the level of MCMV RNA transcription. Undifferentiated PCC4 cells have receptors for MCMV and bind similar amounts of radiolabeled virus as differentiated PCC4 cells. After MCMV binds to its receptors on undifferentiated cells, MCMV penetrates the plasma membrane and is transported to the cells' nuclei. MCMV DNA was present in the cytoplasm, and small amounts of MCMV RNA (less than 17 percent of that found in MCMV-infected differentiated PCC4 cells) were found in the nucleus. However, MCMV RNA was not detected in the cytoplasm of undifferentiated cells. A latent infection was established by infecting undifferentiated PCC4 cells with MCMV, inactivating residual infectivity with antibodies to MCMV, and propagating cells under conditions that maintained the undifferentiated state. These MCMV-infected undifferentiated cells did not produce infectious virus, viral antigens, or viral RNA but did contain viral DNA detectable by DNA-DNA hybridization kinetics. Latency was terminated and infectious virus was made when such undifferentiated cells were induced to differentiate.
Vaccine for Prevention of Mild and Moderate-to-Severe Influenza in Children
Authors: Varsha K. Jain, Luis Rivera, Khalequ Zaman, Roberto A. Espos, Chukiat Sirivichayakul, Beatriz P. Quiambao, Doris M. Rivera-Medina, Pirunghul Kerdpanich, Mehmet Ceyhan, Ener C. Dinleyici, Alejandro Cravioto, Mohammed Yunus, Pornthep Chanthavanich, Kriengsak Limkittikul, Zafer Kurugol, Emre Alhan, Adrian Caplanusi, Serge Durviaux, Philippe Boutet, Opokua Ofori-Anyinam, Vijayalakshmi Chandrasekaran, Ghassan Dbaibo, Bruce L. Innis
Journal: New England Journal of Medicine (2013)

Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages.In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group).In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%).The QIV was efficacious in preventing influenza in children. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).
Prevalence and risk determinants of HIV-1 and HIV-2 infections in pregnant women in Bissau
Authors: Erika Gianelli, Agostino Riva, Fanny A. Rankin Bravo, David Da Silva Te, Enrica Mariani, Giovanni Casazza, Chiara Scalamogna, Oscar Bosisio, Fulvio Adorni, Stefano Rusconi, Massimo Galli
Journal: Journal of Infection (2010)
Hormone Activity of Hydroxylated Polybrominated Diphenyl Ethers on Human Thyroid Receptor-β: <i>In Vitro</i> and <i>In Silico</i> Investigations
Authors: Fei Li, Qing Xie, Xuehua Li, Na Li, Ping Chi, Jingwen Chen, Zijian Wang, Ce Hao
Journal: Environmental Health Perspectives (2009)

Hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disrupt thyroid hormone status because of their structural similarity to thyroid hormone. However, the molecular mechanisms of interactions with thyroid hormone receptors (TRs) are not fully understood.We investigated the interactions between HO-PBDEs and TRbeta to identify critical structural features and physicochemical properties of HO-PBDEs related to their hormone activity, and to develop quantitative structure-activity relationship (QSAR) models for the thyroid hormone activity of HO-PBDEs.We used the recombinant two-hybrid yeast assay to determine the hormone activities to TRbeta and molecular docking to model the ligand-receptor interaction in the binding site. Based on the mechanism of action, molecular structural descriptors were computed, selected, and employed to characterize the interactions, and finally a QSAR model was constructed. The applicability domain (AD) of the model was assessed by Williams plot.The 18 HO-PBDEs tested exhibited significantly higher thyroid hormone activities than did PBDEs (p < 0.05). Hydrogen bonding was the characteristic interaction between HO-PBDE molecules and TRbeta, and aromaticity had a negative effect on the thyroid hormone activity of HO-PBDEs. The developed QSAR model had good robustness, predictive ability, and mechanism interpretability.Hydrogen bonding and electrostatic interactions between HO-PBDEs and TRbeta are important factors governing thyroid hormone activities.