tbuckley/cabot-search huggingface dataset:
The Emerging Role of Immunosurveillance in Dictating Metastatic Spread in Breast Cancer
Authors: Clare Y. Slaney, Jai Rautela, Belinda S. Parker
Journal: Cancer Research (2013)

Abstract It is now well known that the immune system can recognize transformed cells and control the initiation and growth of some cancers, a process termed tumor immunosurveillance. Key regulators of this process have been described in the primary tumor setting, where the balance of protumor and antitumor responses dictates tumor initiation and progression. Accumulating evidence suggests that immunosurveillance may also be critical for regulating metastatic spread, the most fatal aspect of cancer, and that mechanisms of overcoming immune control may be quite different from those at the primary site. Our recent findings support loss of type I interferon (IFN) signaling as a tumor-cell intrinsic mechanism of evading metastasis-specific immune responses in breast cancer. We revealed that type I IFN-induced innate (natural killer) and adaptive (CD8+ T cell) responses suppressed bone metastatic growth and this was associated with decreased accumulation of immune suppressor cells (myeloid-derived suppressor cells). This review summarizes recent findings that are in support of tumor-induced immunosurveillance in regulating metastatic spread, including evidence that immune regulation of primary tumors may be distinct from those dictating metastasis. Cancer Res; 73(19); 5852–7. ©2013 AACR.
Does Intermittent Mandatory Ventilation Accelerate Weaning?
Authors: E. Neil Schachter, Duane Tucker, Gerald J. Beck
Journal: JAMA (1981)

Intermittent mandatory ventilation (IMV) was introduced to facilitate the weaning of patients from mechanical ventilation. The outcome of ventilator management in 116 patients who were treated in the first three months of 1975 was compared retrospectively with that of 135 patients who were treated in the first three months of 1976. All patients who were treated in 1975 received conventional (assisted or controlled) mechanical ventilation. In 1976, seventy-seven patients (57%) were treated with the use of IMV, and 58 (43%) were treated with the use of conventional mechanical ventilation. Sixty-five patients who were treated in 1976 with the use of IMV were matched with patients who were treated in 1975 with the use of conventional ventilation, on the basis of age, sex, race, history of pulmonary disease, smoking history, diagnosis, service, and location of therapy. The average time spent on a ventilator by the IMV patients was 145 hours, whereas the matched control patients spent 142 hours. The length of hospitalization was 36 days for the IMV patients and 30 days for the control patients. These time periods were not significantly different and indicate that IMV did not reduce the length of ventilator management. (<i>JAMA</i>1981;246:1210-1214)
Globin synthesis in fractionated Normoblasts of beta-thalassemia heterozygotes.
Authors: W G Wood, G Stamatoyannopoulos
Journal: Journal of Clinical Investigation (1975)

Globin chain synthesis was examined in erythroid cells of increasing maturity, fractionated from the whole bone marrow of beta-thalassemia heterozygotes by a density gradient centrifugation procedure. In experiments using total cell "globin," a gradient of alpha/beta chain ratios was observed, increasing with erythroid cell maturation from unity in the basophilic cells up to 2.0 in reticulocytes. Gel filtration of the lysates from these marrow fractions revealed the presence of free alpha chains even in the most immature cells, the amount of which increased with erythroid cell age; the total alpha/beta ratio derived from gel filtration experiments showed a gradient similar to that observed in the total globin experiments. However, the alpha/beta ratio of the hemoglobin fraction obtained by gel filtration remained constant throughout maturation at an average of 0.65. This latter finding is incompatible with balanced synthesis at any stage of red cell development and excludes the possibility that total beta chain production is higher in the early cells than in the later cells or that alpha chain production in the early cells is reduced to the level of beta chain synthesis. Furthermore, in a Hb S/beta-thalassemia marrow examined, the beta A/beta S ratio remained constant throughout maturation while the alpha/non-alpha ratio showed an increase like that observed in the simple beta-thalassemia heterozygotes. This argues strongly against increased synthesis from either the thalassemic or nonthalassemic beta chain gene being responsible for the balanced synthesis in the immature cells. These findings lead us to suggest that, in beta-thalassemia heterozygotes, a large alpha chain pool is present throughout erythroid cell maturation and that the observed increase in alpha/beta ratios is a function of the ability of those cells to degrade the excess alpha chains.
Identification of a Cytokine-induced Antiapoptotic Molecule Anamorsin Essential for Definitive Hematopoiesis
Authors: Hirohiko Shibayama, Emi Takai, Itaru Matsumura, Michiyoshi Kouno, Eiichi Morii, Yukihiko Kitamura, Junji Takeda, Yuzuru Kanakura
Journal: The Journal of Experimental Medicine (2004)

Many growth factors and cytokines prevent apoptosis. Using an expression cloning method, we identified a novel antiapoptotic molecule named Anamorsin, which does not show any homology to known apoptosis regulatory molecules such as Bcl-2 family, caspase family, or signal transduction molecules. The expression of Anamorsin was completely dependent on stimulation with growth factors such as interleukin 3, stem cell factor, and thrombopoietin in factor-dependent hematopoietic cell lines, and forced expression of Anamorsin conferred resistance to apoptosis caused by growth factor deprivation in vitro. Furthermore, Anamorsin was found to act as an antiapoptotic molecule in vivo because Anamorsin−/− mice die in late gestation due to defective definitive hematopoiesis in the fetal liver (FL). Although the number of hematopoietic stem/progenitor cells in the FL did not decrease in these mice, myeloid, and particularly erythroid colony formation in response to cytokines, was severely disrupted. Also, Anamorsin−/− erythroid cells initiated apoptosis during terminal maturation. As for the mechanism of Anamorsin-mediated cell survival, a microarray analysis revealed that the expression of Bcl-xL and Jak2 was severely impaired in the FL of Anamorsin−/− mice. Thus, Anamorsin is considered to be a necessary molecule for hematopoiesis that mediates antiapoptotic effects of various cytokines.
Health Effects of Chronic Pesticide Exposure: Cancer and Neurotoxicity
Authors: Michael C.R. Alavanja, Jane A. Hoppin, Freya Kamel
Journal: Annual Review of Public Health (2004)

Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers.
Leucine-rich repeat kinase 2 and alpha-synuclein: intersecting pathways in the pathogenesis of Parkinson's disease?
Authors: Elisa Greggio, Marco Bisaglia, Laura Civiero, Luigi Bubacco
Journal: Molecular Neurodegeneration (2011)

Although Parkinson's disease (PD) is generally a sporadic neurological disorder, the discovery of monogenic, hereditable forms of the disease has been crucial in delineating the molecular pathways that lead to this pathology. Genes responsible for familial PD can be ascribed to two categories based both on their mode of inheritance and their suggested biological function. Mutations in parkin, PINK1 and DJ-1 cause of recessive Parkinsonism, with a variable pathology often lacking the characteristic Lewy bodies (LBs) in the surviving neurons. Intriguingly, recent findings highlight a converging role of all these genes in mitochondria function, suggesting a common molecular pathway for recessive Parkinsonism. Mutations in a second group of genes, encoding alpha-synuclein (α-syn) and LRRK2, are transmitted in a dominant fashion and generally lead to LB pathology, with α-syn being the major component of these proteinaceous aggregates. In experimental systems, overexpression of mutant proteins is toxic, as predicted for dominant mutations, but the normal function of both proteins is still elusive. The fact that α-syn is heavily phosphorylated in LBs and that LRRK2 is a protein kinase, suggests that a link, not necessarily direct, exists between the two. What are the experimental data supporting a common molecular pathway for dominant PD genes? Do α-syn and LRRK2 target common molecules? Does LRRK2 act upstream of α-syn? In this review we will try to address these of questions based on the recent findings available in the literature.
Inhibition of rupture of established atherosclerotic plaques by treatment with apolipoprotein A-I
Authors: G. J. Reimers, C. L. Jackson, J. Rickards, P. Y. Chan, J. S. Cohn, K.-A. Rye, P. J. Barter, K. J. Rodgers
Journal: Cardiovascular Research (2011)

Plasma concentrations of high-density lipoprotein (HDL)-cholesterol correlate inversely with the incidence of myocardial infarction in humans. We investigated the effect of treatment with human apolipoprotein A-I (apoA-I), the principal protein of HDL, on plaque disruption in an animal model.Seventy apolipoprotein E knockout mice were induced to develop atherosclerotic lesions in the brachiocephalic artery by feeding a high-fat diet for 9 weeks. Mice then received twice-weekly treatment with human apoA-I (8 mg/kg) or vehicle, for 2 weeks. The incidence of acute plaque disruption was reduced by 65% in mice receiving apoA-I (P < 0.01). Plaques in treated mice had a more stable phenotype, with an increase in smooth muscle cell (SMC): macrophage ratio (P = 0.05), principally the consequence of an increase in the number of SMC in plaques. In the fibrous cap, there were reductions in matrix metalloproteinase-13 (-69%, P < 0.0001) and S100A4, a marker of SMC de-differentiation (-60%, P < 0.0001). These results indicate that 2 weeks of treatment with small amounts of human apoA-I produces more stable plaques in a mouse model.Treatment with apoA-I has the potential to stabilize plaques and prevent plaque rupture in humans.
Arthritis Associated with Ulcerative Colitis: A Clinical and Pathological Study
Authors: E. G. L. Bywaters, B. M. Ansell
Journal: Annals of the Rheumatic Diseases (1958)

<h3>Background</h3> PWID engaged in unconventional sexual behaviour run the greater risk of becoming HIV infected due to multiple sexual and injecting risks. We sought to test the sexual health indicators (SHI) developed by UNAIDS/WHO and understand the impact of attitude on risk behaviour of PWID. <h3>Method</h3> RDS was used in a cross sectional survey to recruit 500 PWID in August-October 2012 in Barnaul, Russia. One of the composite SHIs defined as "Conformity with traditional social norms concerning gender and sexuality among men and women 15+" included a question "Homosexuality is normal diversity of sexuality". Respondents should either "Agree" or "Disagree" with the above statement. RDSAT was used to calculated point estimates. <h3>Results</h3> Response rate was 94.2%. More than a half of all participants reported incarceration history (60.3%, 95% CI 55.2, 65.4) and coverage by prevention programmes (64.2%, 95% CI 58.3, 69.7). Majority (90.7%, 95% CI 85.4, 90.4) disagreed with statement: 96.0% (95% CI 91.4.98.7) of men and 79.4%(95% CI 67.5.90.20) of women. Young female PWID (&lt; 30 years) had highest proportion of negative attitude (94.4%, 95% CI 89.1, 99.1) among all age groups. Positive attitude among PWID who reported no incarceration was 13.9% (95% CI 7.5, 21.9) and who had been incarcerated 2.9% (95% CI 0.8, 5.1). 82.6% (95% CI 72.1, 92.7) of women at 30–39 had negative attitude. 66.3% (95% CI 51.4, 77.7) of female PWID who disagreed did not use condom at last sexual contact while those who agreed - 17.5% (95% CI 5.8, 31.4). In comparison with women 2.9% (95% CI0.1, 8.1) of men PWID who agreed did not use condom. <h3>Conclusions</h3> History of incarceration correlates with negative attitude towards non-traditional sexual orientation as well as condom use by PWID. Further research is necessary to understand social determents and behavioural factors and develop adequate interventions.
Antibiotic Therapy After Acute Myocardial Infarction
Authors: Ralf Zahn, Steffen Schneider, Birgit Frilling, Karlheinz Seidl, Ulrich Tebbe, Michael Weber, Martin Gottwik, Ernst Altmann, Friedrich Seidel, Jürgen Rox, Ulrich Höffler, Karl-Ludwig Neuhaus, Jochen Senges
Journal: Circulation (2003)

Infection with Chlamydia pneumoniae is suspected to contribute to the pathogenesis of human atherosclerosis. We investigated whether treatment with the macrolide antibiotic roxithromycin would reduce mortality or morbidity in patients with an acute myocardial infarction.Eight hundred seventy-two patients with an acute myocardial infarction (AMI) were randomly assigned to receive double-blind treatment with either 300 mg roxithromycin or placebo daily for 6 weeks. Primary end point was total mortality during 12-month follow-up. Four hundred thirty-three patients were treated with roxithromycin and 439 with placebo. With the exception of a higher proportion of patients suffering an anterior wall AMI (48.1% in the roxithromycin group versus 40.2% in the placebo group; P=0.027) and a lower prevalence of chronic obstructive pulmonary disease in the roxithromycin group (3.5% versus 6.9%, P=0.028), baseline characteristics, reperfusion therapy, and medical treatment were well balanced between the two groups. More patients in the roxithromycin group interrupted their study medication before completion of at least 4 weeks of treatment (78 of 433 [18%] versus 48 of 439 [11%]; P=0.003; odds ratio, 1.8; 95% CI, 1.2 to 2.6). Follow-up at 12 months was achieved in 868 of 872 (99.5%) patients. Total mortality at 12 months was 6.5% (28 of 431) in the roxithromycin group compared with 6.0% (26 of 437) in the placebo group (odds ratio, 1.1; 95% CI, 0.6 to 1.9; P=0.739). There were also no differences in the secondary combined end points at 12 months.Treatment of AMI patients with roxithromycin did not reduce event rates during 12 months of follow-up. Therefore, our findings do not support the routine use of antibiotic treatment with a macrolide in patients with AMI.
Evaluation of the TB strain typing service in England: Initial findings
Authors: Jessica Mears
Journal: European Respiratory Journal (2012)

Background  In 2010 a universal Tuberculosis (TB) Strain Typing Service (STS) was initiated across England to contribute to national TB surveillance and control by detecting TB clusters early, informing public health action, and estimating rates of recent transmission (RT) and false positive (false+) TB isolation. A multi-disciplinary evaluation group was formed to prospectively evaluate the STS. We report results of primary outputs along with user satisfaction (UsS) with the service.   Methods  a) All 24 MIRU-VNTR strain types (ST) between January-December 2010 were used to estimate the proportion of clustered cases in England in the first year of the STS. The n-1 method was used to estimate rates of RT. Regional and demographic differences were explored. b) Prospective data on suspected false+ TB isolates were collected from the TB reference laboratories between October 2010-2011. c) A two-part self-completion survey was implemented in December 2010 and March 2012 to establish change in uptake and UsS with the STS.   Results  a) 3577 TB patients had at least 22 MIRU-VNTR loci typed. 39.6% (n=1408) were clustered into 422 clusters of at least 2 cases. RT was estimated to be 27.7%. b) 5887 TB isolates were typed. 47 isolates were suspected of being false+ because of their ST. 15 (0.25%) isolates were confirmed false+ by ST. c) 14.7% of the 258 respondents at baseline had not heard of the STS and 23.2% never used it. Of respondents that used the STS, 55.7% found ST data quite useful, 39.7% very useful. A comparative analysis of the surveys will be presented.   Conclusions  The STS will improve as a public health tool when it is fully-implemented and more data becomes available. The evaluation of the STS is ongoing.
Drug-eluting versus bare-metal stents in saphenous vein graft lesions (ISAR-CABG): a randomised controlled superiority trial
Authors: Julinda Mehilli, Jürgen Pache, Mohamed Abdel-Wahab, Stefanie Schulz, Robert A Byrne, Klaus Tiroch, Jörg Hausleiter, Melchior Seyfarth, Ilka Ott, Tareq Ibrahim, Massimiliano Fusaro, Karl-Ludwig Laugwitz, Steffen Massberg, Franz-Josef Neumann, Gert Richardt, Albert Schömig, Adnan Kastrati
Journal: The Lancet (2011)
A Novel Method to Detect Proteins Evolving at Correlated Rates: Identifying New Functional Relationships between Coevolving Proteins
Authors: Nathaniel L. Clark, Charles F. Aquadro
Journal: Molecular Biology and Evolution (2009)

Interacting proteins evolve at correlated rates, possibly as the result of evolutionary pressures shared by functional groups and/or coevolution between interacting proteins. This evolutionary signature can be exploited to learn more about protein networks and to infer functional relationships between proteins on a genome-wide scale. Multiple methods have been introduced that detect correlated evolution using amino acid distances. One assumption made by these methods is that the neutral rate of nucleotide substitution is uniform over time; however, this is unlikely and such rate heterogeneity would adversely affect amino acid distance methods. We explored alternative methods that detect correlated rates using protein-coding nucleotide sequences in order to better estimate the rate of nonsynonymous substitution at each branch (d(N)) normalized by the underlying synonymous substitution rate (d(S)). Our novel likelihood method, which was robust to realistic simulation parameters, was tested on Drosophila nuclear pore proteins, which form a complex with well-documented physical interactions. The method revealed significantly correlated evolution between nuclear pore proteins, where members of a stable subcomplex showed stronger correlations compared with those proteins that interact transiently. Furthermore, our likelihood approach was better able to detect correlated evolution among closely related species than previous methods. Hence, these sequence-based methods are a complementary approach for detecting correlated evolution and could be applied genome-wide to provide candidate protein-protein interactions and functional group assignments using just coding sequences.
A bloody mess: scalp lump misidentified
Authors: Chern Beverly Brenda Lim, Vikas Khanduja, Jo-Anne Chin Aleong, Michael Douek
Journal: Journal of the Royal Society of Medicine (2005)

Angiolymphoid hyperplasia with eosinophilia is seldom diagnosed preoperatively. When excising what seems to be a sebaceous cyst, the surgeon can be caught out by unexpected haemorrhage.
Elevated -fetoprotein and a pancreatic tumour
Authors: K-L Liu, Y-C Teng, Y-W. Tien, J-T Lin
Journal: Gut (2007)

A 47-year-old man without any discomfort was found to have elevated serum α-fetoprotein (AFP) of 41.0 ng/ml (normal range <20 ng/ml) during a health check-up in January 2000. Physical examination and laboratory data were non-contributory except …
Dimensions and Geometric Relationships of the Human Aortic Value as a Function of Pressure
Authors: W. MILTON SWANSON, RICHARD E. CLARK
Journal: Circulation Research (1974)

In a continuing effort to develop improved prosthetic heart valves, a redefinition of the anatomy of the human aortic valve as a function of stress was undertaken. Dimensions and geometric relationships of the human aortic valve as a function of intraaortic pressure between 0 and 120 mm Hg were obtained from a series of silicone rubber valve casts. The axial length of the valve region was found to vary negligibly with pressure, but significant variations in geometry and angular dimensions were seen. The leaflet attachment annulus forms an ellipse at the plane of intersection with the cylindrical surface passing from the left ventricular tract through the aorta. Deductions from stress considerations for the measured geometry indicate that the loaded leaflet is a section of a cylindrical surface. The equation for this developed surface was obtained, and a prosthetic design was determined using average values at 100 mm Hg. The leaflet is developable onto a plane with a cut required along part of the junction line between the initially cylindrical part and the plane coapting surfaces. Optimum valve shape mandates a base angle between the cylindrical leaflet and the center axis of 70° (α =20-22°, where α is the leaflet angle).
Demonstration of a pH gradient across mucus adherent to rabbit gastric mucosa: evidence for a 'mucus-bicarbonate' barrier.
Authors: S E Williams, L A Turnberg
Journal: Gut (1981)

We examined the ability of the mucus layer adherent to isolated pieces of rabbit gastric mucosa to maintain a pH gradient across it. Using antimony microelectrodes, a stable pH gradient was detected from pH 2.31 +/- 0.04 on the luminal side to pH 7.26 +/- 0.15 (n = 22) on the epithelial side of the mucus layer. The gradient was maintained for at least 60 minutes. A metabolic inhibitor, potassium cyanide, markedly reduced the tissues9 ability to maintain this pH gradient, suggesting involvement of an active cellular process, probably that of bicarbonate secretion. These observations provide additional evidence in favour of a 9mucus-bicarbonate9 barrier which may be of importance in protecting the underlying gastric mucosa.
Sudden death and sport--preventable or inevitable.
Authors: D. Tunstall Pedoe
Journal: British Journal of Sports Medicine (1984)

Is exercising a normal human activity, like eating, drinking, copulating and defaecating or is it something only to be sampled under doctors orders, a dangerous medicine?Recent press publicity given to the death of Jim Fixx and Bruce Davies' presentation to the British Association for the Advancement of Science might suggest the latter.