tbuckley/cabot-search huggingface dataset:
TRIF mobilizes unique primary defense against Gram-negative bacteria in intestinal interface
Authors: John Sotolongo, Saravana Kanagavelu, Jinhee Hyun, Jose Ruiz, Masayuki Fukata
Journal: Gut Microbes (2012)

The gastrointestinal tract is the largest mucosal surface in our body. It houses diverse microorganisms that collectively form the commensal microbial community. The security of this community is kept by host-microbial interactions and is violated by foreign pathogens that induce local as well as systemic pathology. In most cases, gastrointestinal infections are caused by Gram-negative enteropathogens, which trigger host immune responses through the TLR4 signaling pathways. Although TRIF is one of the major pathways downstream of TLR4, very little is known about how the TRIF pathway contributes to intestinal defense against pathogenic infection. Recently, we reported a unique role of TRIF signaling in host response to an enterophathogen Yersinia enterocolitica, which consisted of IFN-β induction from regional macrophages followed by activation of NK cells in the mesenteric lymph nodes. In this addendum, we show distinct roles for TRIF-dependent host response in intestinal vs. systemic infection with Gram-negative enterophathogens.
Physicochemical Evolution and Molecular Adaptation of the Cetacean and Artiodactyl Cytochrome b Proteins
Authors: D. A. McClellan, E. J. Palfreyman, M. J. Smith, J. L. Moss, R. G. Christensen, J. K. Sailsbery
Journal: Molecular Biology and Evolution (2004)

Cetaceans have most likely experienced metabolic shifts since evolutionarily diverging from their terrestrial ancestors, shifts that may be reflected in the proteins such as cytochrome b that are responsible for metabolic efficiency. However, accepted statistical methods for detecting molecular adaptation are largely biased against even moderately conservative proteins because the primary criterion involves a comparison of nonsynonymous and synonymous substitution rates (dN/dS); they do not allow for the possibility that adaptation may come in the form of very few amino acid changes. We apply the MM01 model to the possible molecular adaptation of cytochrome b among cetaceans because it does not rely on a dN/dS ratio, instead evaluating positive selection in terms of the amino acid properties that comprise protein phenotypes that selection at the molecular level may act upon. We also apply the codon-degeneracy model (CDM), which focuses on evaluating overall patterns of nucleotide substitution in terms of base exchange, codon position, and synonymy to estimate the overall effect of selection. Using these relatively new models, we characterize the molecular adaptation that has occurred in the cetacean cytochrome b protein by comparing revealed amino acid replacement patterns to those found among artiodactyls, the modern terrestrial mammals found to be most closely related to cetaceans. Our findings suggest that several regions of the cetacean cytochrome b protein have experienced molecular adaptation. Also, these adaptations are spatially associated with domain structure, protein function, and the structure and function of the cytochrome bc1 complex and its constituents. We also have found a general correlation between the results of the analytical software programs TreeSAAP (which implements the MM01 model) and CDM (which implements the codon-degeneracy model).
Epidemiology of research into interventions for the treatment of osteoarthritis of the knee joint
Authors: J. A Chard
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> To assess the published research base for interventions for osteoarthritis of the knee, and to identify areas in need of further research. <h3>METHODS</h3> Literature searches were conducted on electronic databases (Medline, Embase, ISI, and Cochrane library), bibliographies of existing review articles were hand searched, and a postal questionnaire was sent to members of the Osteoarthritis Research Society International. All relevant articles were copied and searched for treatment type, study methodology, statistical results, conclusions, funding source, researcher affiliations, and year of publication, using a predetermined data extraction form. <h3>RESULTS</h3> There have been marked changes in the literature over the period studied (1950–98), with a recent rise in trials of physical therapy, educational interventions, and complementary treatments. However, overall, most research was either drug (59.1%) or surgically (25.6%) related. Most of the studies reported positive results (94%). Research on oral drugs was significantly more likely to provide a positive result than research on any other intervention (p&lt;0.001 by χ<sup>2</sup> test). Commercially funded studies were significantly more likely to produce a positive result than non-commercially funded research (p=0.0027 by χ<sup>2</sup> test). <h3>CONCLUSIONS</h3> Analysis of time trends indicates that the research agenda does shadow changes in consumer demands. However, there are significant gaps in the research base that need to be considered.
Determination of cyclovirobuxine D in human plasma by liquid chromatography tandem mass spectrometry and application in a pharmacokinetic study
Authors: Ling-li Mu, Peng Yu, Li-hua He
Journal: Acta Pharmaceutica Sinica B (2011)

A sensitive and reliable method based on liquid chromatography tandem mass spectrometry (LC–MS/MS) for the quantitation of cyclovirobuxine D in human plasma has been developed and validated. Sample preparation by solid phase extraction was followed by separation on a CN column with a mobile phase of methanol–water (95:5, v/v) containing 0.2% formic acid. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (SRM) of the transitions at m/z 403.0→372.0 for cyclovirobuxine D and m/z 325.0→234.0 for citalopram (internal standard). The method was linear in the range 10–200 ng/L with LLOQ of 10 ng/L, recovery >85%, and no significant matrix effects. Intra- and inter-day precisions were all <9% with accuracies of 94.0–104.8%. The method was successfully applied to a pharmacokinetic study involving a single oral administration of a 2 mg cyclovirobuxine D tablet to twenty-two healthy Chinese volunteers.
Cytogenetic markers of susceptibility: influence of polymorphic carcinogen-metabolizing enzymes.
Authors: H Norppa
Journal: Environmental Health Perspectives (1997)

Polymorphisms of xenobiotic-metabolizing enzymes, responsible for individual differences in metabolic activation and detoxification reactions, may profoundly modulate the effects of chemical carcinogens. In the case of genotoxic carcinogens, differences in biological effects due to genetic polymorphisms can be evaluated by cytogenetic methods such as the analysis of chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), micronuclei (MN), and changes in chromosome number. These techniques can be applied to any exposure known to induce such alterations, without additional method development for each exposing agent. The influence of polymorphic genes on the cytogenetic effects of a carcinogen can quickly be tested in vitro using metabolically competent cells collected from donors representing different genotypes or phenotypes. For instance, erythrocytes from individuals positive for glutathione S-transferase T1 (GSTT1) express GSTT1, whereas GSTT1-null donors, having a homozygous deletion of the GSTT1 gene, completely lack this detoxification enzyme. This deficiency results in highly increased sensitivity to SCE induction in whole-blood lymphocyte cultures by 1,2:3,4-diepoxybutane, a reactive metabolite of 1,3-butadiene. The same cytogenetic techniques can also be applied as effect biomarkers in studies of human populations exposed to genotoxic carcinogens. For example, elevated rates of chromosome damage have been detected among smokers lacking glutathione S-transferase M1 (GSTM1-null genotype), and the baseline level of SCEs seems to be increased in GSTT1-null individuals. Information obtained from cytogenetic studies of genetic polymorphisms can be used, for example, to recognize the genotoxically relevant substrates of the polymorphic enzymes, to identify genotypes that are susceptible to these genotoxins, to improve in vitro genotoxicity tests utilizing human cells, to increase the sensitivity of cytogenetic endpoints as biomarkers of genotoxic effects in humans, and to direct mechanistic studies and cancer epidemiology.
REPEATED PERFORATIONS OF PEPTIC ULCERS WITH RECOVERY
Authors: S. Paul Ehrlich
Journal: JAMA (1928)

A case of repeated perforations of peptic ulcers with recovery is here presented because of the rarity with which one can trace the same patient through three perforations occurring at three different sites and on three separate occasions. A review of the literature<sup>1</sup>reveals frequent multiple perforations and an occasional consecutive perforation. <h3>REPORT OF CASE</h3> The history of the patient dates back to 1920, when he was 16 years of age. At this time he began to have epigastric distress following meals, which was relieved by food and sodium bicarbonate. His symptoms continued as epigastric distress for about one and a half years, when they became more severe and more or less constant. This continued until Feb. 16, 1923, when he was seized with an acute attack of epigastric pain. He was taken to the Cook County Hospital, Chicago,<sup>2</sup>where he was found to be suffering from a
The Physician and the Law
Authors: C. B. Scrignar
Journal: JAMA (1967)

Physicians and members of the legal profession who participate in lunacy or sanity hearings to determine a defendant's mental competency to stand trial can unwittingly interfere with due process of law. Four case histories illustrate situations in which this can occur. Failure to recognize the continuous but separated stages of criminal procedure (pretrial, trial, and post-trial) and attempts to resolve trial and post-trial issues at the pretrial stage are perhaps the most common reasons why some inequities do occur. More mutual involvement, interaction, and cross-education between the professions of medicine and law are needed to arrive at solutions to existing problems in these areas.
Transfer of 15-lipoxygenase gene into rabbit iliac arteries results in the appearance of oxidation-specific lipid-protein adducts characteristic of oxidized low density lipoprotein.
Authors: S Ylä-Herttuala, J Luoma, H Viita, T Hiltunen, T Sisto, T Nikkari
Journal: Journal of Clinical Investigation (1995)

Oxidized low density lipoprotein (LDL) possesses several atherogenic properties. The mechanisms by which LDL becomes oxidized in vivo remain unknown, but previous studies have suggested that 15-lipoxygenase may be one of the factors involved in the initiation of LDL oxidation in the arterial wall. 3 wk after a retrovirus-mediated 15-lipoxygenase gene transfer into iliac arteries of normocholesterolemic rabbits there was a threefold increase in 15-lipoxygenase activity but no signs of LDL oxidation. However, when animals were made moderately hypercholesterolemic by feeding a 0.13% cholesterol diet for 2-3 wk starting from day 4 after the gene transfer, oxidation-specific lipid-protein adducts characteristic of oxidized LDL were detected in 15-lipoxygenase-transduced arteries. Control experiments in which contralateral iliac arteries were transduced with beta-galactosidase-containing retroviruses showed only occasional signs of the presence of oxidation-specific adducts. The results support the hypothesis that products derived from the 15-lipoxygenase activity are involved in the induction of LDL oxidation within the arterial wall, provided that sufficient concentrations of lipoproteins are present in the artery.
Rocky in suburbia
Authors: Des Spence
Journal: BMJ (2006)

As students we watched Rocky IV on video rather than go to histology; somehow it just seemed more relevant. Against all international advice Rocky agrees to fight in the former Soviet Union. Once there, the Italian stallion is denied proper training facilities and resorts to chopping logs, running in the snow, and pulling carts, all to the tune of spandex rock.

His Russian opponent is seen in a hi-tech gym being pumped with steroids while …
DIAGNOSIS AND TREATMENT OF HEAD INJURIES
Authors: ERNEST SACHS
Journal: JAMA (1923)

I am presenting this subject again when so much has already been written about it because I find, after talking with others and noting what others have said, that there still remains the greatest confusion both as regards the classification and the treatment of this very frequent injury. In presenting this subject to my students I have for years eliminated as far as possible many of the theoretical considerations in order to bring out as clearly as possible a concrete, practical, simple and, I believe, logical method of dealing with these cases. The plan here outlined is the one I have followed for the last ten years; and though my series is not very large, the cases have been studied with a good deal of care and with due consideration for the methods that from time to time have been suggested by others.  Some authorities have laid great stress on
Judge may report drug company executive to attorney general
Authors: C. Dyer
Journal: BMJ (2004)

A high court judge is considering reporting a senior executive of GlaxoSmithKline to the attorney general after he told an expert witness appearing for the company's opponents in a patent action that the company would not fund any research by him in the future.

Mr Justice Pumfrey, who was last week hearing a patent action brought against Glaxo by a group of generic drug companies over Seretide, its combined inhaler of salmeterol and fluticasone, called Dr Garth Rapeport before him for questioning.

The judge acted after Professor Clive Page, an asthma expert from King's College, London, who was appearing as a witness …
Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada
Authors: Danuta M. Skowronski, Gaston De Serres, Natasha S. Crowcroft, Naveed Z. Janjua, Nicole Boulianne, Travis S. Hottes, Laura C. Rosella, James A. Dickinson, Rodica Gilca, Pam Sethi, Najwa Ouhoummane, Donald J. Willison, Isabelle Rouleau, Martin Petric, Kevin Fonseca, Steven J. Drews, Anuradha Rebbapragada, Hugues Charest, Marie-Ève Hamelin, Guy Boivin, Jennifer L. Gardy, Yan Li, Trijntje L. Kwindt, David M. Patrick, Robert C. Brunham
Journal: PLoS Medicine (2010)

In three case-control studies and a household transmission cohort, Danuta Skowronski and colleagues find an association between prior seasonal flu vaccination and increased risk of 2009 pandemic H1N1 flu.
Microparticles in Angiogenesis
Authors: Maria Carmen Martinez, Ramaroson Andriantsitohaina
Journal: Circulation Research (2011)

Considered during the past decades as cell dust, microparticles are now deemed true biomarkers and vectors of biological information between cells. Depending on their origin, the composition of microparticles varies and the subsequent message transported by them, such as proteins, mRNA, or miRNA, can differ. Recent studies have described microparticles as “cargos” of deleterious information in blood vessel wall under pathological situations such as hypertension, myocardial infarction, and metabolic syndrome. In addition, it has been reported that depending on their origin, microparticles also possess a therapeutic potential regarding angiogenesis. Microparticles can act directly through the interaction ligand/receptor or indirectly on angiogenesis by modulating soluble factor production involved in endothelial cell differentiation, proliferation, migration, and adhesion; by reprogramming endothelial mature cells; and by inducing changes in levels, phenotype, and function of endothelial progenitor cells. This results in an increase in formation of in vitro capillary-like tubes and the generation of new vessels in vivo under ischemic conditions, for instance. Taking into consideration these properties of microparticles, recent evidence provides new basis to expand the possibility that microparticles might be used as therapeutic tools in pathologies associated with an alteration of angiogenesis.
Immune recognition of OxLDL in atherosclerosis
Authors: John F. Kearney
Journal: Journal of Clinical Investigation (2000)

The innate nonadaptive immune system plays a crucial role in the acute response to infectious agents. Within hours of exposure to an invading microorganism, well before adaptive cellular or humoral immune responses are engaged, the bulk of most infections is cleared by cells and molecules that bind with broad specificity to structures common to various pathogens. Only when infectious organisms break through these barriers do antigen receptor–bearing effector cells of the adaptive immune system come into play, ensuring that these organisms are cleared.

Blurring the distinction between the innate and the cognate aspects of the immune system are subsets of lymphocytes that recognize pathogenic determinants and are expressed even in immunologically naive animals (1). The significance of these lymphocytes is shown by the strong protection, elicited by T-independent natural IgM antibody, against certain viral and bacterial infections (2). The B- or T-cell receptors of these lymphocytes often contain highly conserved sequences, arise reproducibly in all mice, and do not depend on exogenous antigen for their generation. In this respect, they constitute an “evolutionary memory” and form a bridge between pattern recognition molecules — mannose receptors, macrophage scavenger receptors, and other similar molecules (3) — and the classic adaptive responses, which generally require T-cell help both to hone the specificity of the molecular interaction and to maintain immunological memory. These evolutionarily conserved responses to ubiquitously expressed microbial components are not confined to B cells, as there are numerous examples of αβ and γδ T cells that express canonical receptors to microbial components (4, 5).

In this issue of the JCI, Shaw et al. (6) show that these structurally distinct receptors functioning in different branches of the immune system nonetheless share patterns of ligand specificity. This provocative finding not only suggests mechanisms that may influence the progression of the disease, but also identifies a hitherto unknown function of an antibody response to a pathogenic bacterium.
997 RETROSPECTIVE ANALYSIS OF 191 PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA TREATED WITH TRANSARTERIAL CHEMOEMBOLISATION (TACE): VALIDATION OF THE ESTABLISHED AND CONSTRUCTION OF AN IMPROVED HCC-STAGING-SYSTEM
Authors: M. op den Winkel, D. Nagel, P. op den Winkel, J. Sappl, G. Straub, R. Lamerz, C. Zech, P. Stieber, F.T. Kolligs
Journal: Journal of Hepatology (2011)
Goals for nutrition in the year 2000
Authors: W. C. Willett
Journal: CA A Cancer Journal for Clinicians (1999)

Ongoing research continues to support the hypothesis that dietary factors significantly influence the incidence of many human malignancies. Despite some conflicting and confusing studies reported over the past two decades, it is becoming increasingly clear that maintenance of a healthy adult weight, through proper balance of caloric intake and physical activity, is key to cancer prevention. Moreover, current nutritional recommendations for the prevention of cancer include increased consumption of fruits and vegetables; reduced consumption of red meat and animal fat; and avoidance of excessive alcohol use. For many individuals, a daily multivitamin that contains folic acid may also be part of a reasonable overall cancer prevention strategy.
Doxycycline-regulated GDNF expression promotes axonal regeneration and functional recovery in transected peripheral nerve
Authors: Antos Shakhbazau, Chandan Mohanty, Dzmitry Shcharbin, Maria Bryszewska, Anne-Marie Caminade, Jean-Pierre Majoral, Jacob Alant, Rajiv Midha
Journal: Journal of Controlled Release (2013)
Epithelioid hemangioendothelioma of the liver
Authors: Keum Ha Choi, Woo Sung Moon
Journal: Clinical and Molecular Hepatology (2013)

Epithelioid hemangioendothelioma is an uncommon vascular tumor of intermediate malignant potential.1-3 Hepatic epithelioid hemangioendothelioma (HEHE), a rare sarcoma of the liver, usually appears as multiple nodules involving both hepatic lobes, and can be misdiagnosed as metastatic carcinoma on the basis of its radiologic manifestations. HEHE is composed of neoplastic endothelial cells that closely resemble epithelial cells, and shows a characteristic zoning phenomenon. At the periphery, the tumor cells infiltrate preexisting sinusoids and terminal hepatic venules. The center reveals a marked desmoplastic stromal reaction with dense sclerosis, and these findings may mimic those of cholangiocarcinoma. Therefore, confirming that the tumor is of vascular origin using immunohistochemical staining for endothelial cell markers is critical for accurately diagnosing HEHE. In this issue, we present a case of HEHE in a 44-year-old woman and discuss the histopathologic findings.
Unilateral hilar or paratracheal adenopathy in sarcoidosis: a study of 38 cases
Authors: R. W. Spann, E. C. Rosenow, R. A. DeRemee, W. E. Miller
Journal: Thorax (1971)

<h3>Objectives</h3> The Marie Curie Cancer Care Delivering Choice Programme (DCP) aims to help palliative patients be cared for in their place of choice. In this study, new palliative care services delivered in two counties in England included end-of-life care coordination centres, an out-of-hours telephone line and discharge in-reach nurses. The study aimed to investigate the impact of DCP on place of death and hospital usage (emergency department (ED) and admissions). <h3>Methods</h3> Retrospective cohort of all eligible palliative patients who died over a 6-month period in two counties (n=3594). Participants were those who died of conditions considered to be eligible for end-of-life care, as defined by the Public Health England National End of Life Care Intelligence Network. The sample included people who did and did not access DCP services. DCP service, hospital admission and ED use data, demographic and death data were collected on all eligible participants. Data were analysed using descriptive statistics and logistic regression. <h3>Results</h3> After adjusting for potential confounders, those using Delivering Choice were at least 30% less likely to die in hospital or have an emergency hospital admission or ED visit in the last 30 or 7 days of life than those who did not. <h3>Conclusions</h3> Recipients of DCP services were less likely to die in or use hospital services. Those considering new ways of providing end-of-life care could explore the possibility of adopting similar services and evaluating the outcomes from patient, carer and system perspectives.
Cannulation of difficult oesophageal strictures with angiographic catheters.
Authors: M S Sharpe, A H Chalmers, K R Gough
Journal: BMJ (1986)

failure was controlled.Variables were reassessed at two, four, eight, and 12 weeks.The patients tolerated the first dose of captopril well, showing a mild transient hypotensive response.One patient had a notable hypotensive response to the first dose but was asymptomatic and improved when her legs were raised.Twelve patients who were taking captopril three times daily at eight weeks had the regimen changed to twice daily.At 12 weeks the median dose of captopril was 75 mg daily in two divided doses.The table shows the haemodynamic measurements at the start and end of the study.The cardiac variables showed a significant improvement, but there was no significant difference between the variables measured when patients were taking captopril three times daily and those when they were taking it twice daily.Four Means (SD) ofimportant variables measured at beginning and end of12 week study Beginning of study End of study Significance Cardiac index (1/min/m2) -2-21 (0-35) 3 09(1O00) p<0005 Stroke volume index (ml/min/m2) 28 04(5170)