tbuckley/cabot-search huggingface dataset:
Adoptive Transfer of β <sub>2</sub> -Glycoprotein I–Reactive Lymphocytes Enhances Early Atherosclerosis in LDL Receptor–Deficient Mice
Authors: Jacob George, Dror Harats, Boris Gilburd, Arnon Afek, Aviv Shaish, Juri Kopolovic, Yehuda Shoenfeld
Journal: Circulation (2000)

It has been proposed that autoimmune factors can influence the progression of atherosclerosis. We have previously shown that immunization of LDL receptor-deficient (LDL-RD mice) with beta(2)-glycoprotein I (beta2GPI; a principal target of "autoimmune" antiphospholipid antibodies) enhances early atherosclerosis. In the present study, we tested the hypothesis that adoptive transfer of beta2GPI-reactive T cells can accelerate fatty streak formation in LDL-RD mice.LDL-RD mice were immunized with human beta2GPI. An additional group of mice were immunized with beta2GPI and boosted with the same antigen 3 weeks later. Control mice with immunized with human serum albumin. Lymphocytes obtained from the draining lymph node cells or from splenocytes of beta2GPI- or human serum albumin-immunized mice were stimulated in vitro with beta2GPI or with the mitogen concavalin A, respectively. The cultured lymphocytes were transferred intraperitoneally to syngenic LDL-RD mice, and the mice were fed a high-fat "Western" diet for 5 weeks until death. Mice injected with lymphocytes from draining lymph nodes or spleens of beta2GPI-immunized animals displayed larger fatty streaks than those induced by control treated animals. T-cell-depleted splenocytes from beta2GPI were unable to promote lesion formation in the mice.The present study provides the first direct evidence for a role of antigen (beta2GPI)-reactive T cells in the promotion of fatty streaks in mice.
Nina Agnes Jane Carson
Authors: Dennis Carson
Journal: BMJ (2007)

After graduation, Nina Carson became a trainee pathologist. An appointment in the laboratory of the Royal Belfast Hospital for Sick Children evolved into a research opportunity in the Department of Child Health, Queen's University, where Nina worked until retirement in 1983.

In 1963 Nina graduated doctor of medicine from studies examining urine for metabolic abnormalities in over 2000 children and adults with mental disability. While identifying a high prevalence of undiagnosed phenylketonuria (PKU), Nina described the clinical and urinary amino acid chromatograph abnormalities in two siblings …
Scavenger Receptor Class B Type I Is a Plasma Membrane Cholesterol Sensor
Authors: Sonika Saddar, Véronique Carriere, Wan-Ru Lee, Keiji Tanigaki, Ivan S. Yuhanna, Sajesh Parathath, Etienne Morel, Manya Warrier, Janet K. Sawyer, Robert D. Gerard, Ryan E. Temel, J. Mark Brown, Margery Connelly, Chieko Mineo, Philip W. Shaul
Journal: Circulation Research (2012)

Signal initiation by the high-density lipoprotein (HDL) receptor scavenger receptor class B, type I (SR-BI), which is important to actions of HDL on endothelium and other processes, requires cholesterol efflux and the C-terminal transmembrane domain. The C-terminal transmembrane domain uniquely interacts with plasma membrane (PM) cholesterol.The molecular basis and functional significance of SR-BI interaction with PM cholesterol are unknown. We tested the hypotheses that the interaction is required for SR-BI signaling, and that it enables SR-BI to serve as a PM cholesterol sensor.In studies performed in COS-M6 cells, mutation of a highly conserved C-terminal transmembrane domain glutamine to alanine (SR-BI-Q445A) decreased PM cholesterol interaction with the receptor by 71% without altering HDL binding or cholesterol uptake or efflux, and it yielded a receptor incapable of HDL-induced signaling. Signaling prompted by cholesterol efflux to methyl-β-cyclodextrin also was prevented, indicating that PM cholesterol interaction with the receptor enables it to serve as a PM cholesterol sensor. Using SR-BI-Q445A, we further demonstrated that PM cholesterol sensing by SR-BI does not influence SR-BI-mediated reverse cholesterol transport to the liver in mice. However, the PM cholesterol sensing does underlie apolipoprotein B intracellular trafficking in response to postprandial micelles or methyl-β-cyclodextrin in cultured enterocytes, and it is required for HDL activation of endothelial NO synthase and migration in cultured endothelial cells and HDL-induced angiogenesis in vivo.Through interaction with PM cholesterol, SR-BI serves as a PM cholesterol sensor, and the resulting intracellular signaling governs processes in both enterocytes and endothelial cells.
Collagen alteration in an animal model of colonic diverticulosis.
Authors: L Wess, M A Eastwood, C A Edwards, A Busuttil, A Miller
Journal: Gut (1996)

BACKGROUND--Changes in the structure and integrity of the colon dependent on collagen content and crosslinkage occur with age. AIMS--This study using an animal model examines colonic collagen content and crosslinkage over the lifetime of rats on fibre deficient and higher fibre diets. METHODS--Two groups of 20 rats were fed either a fibre deficient diet (1.7 g NSP (non-starch polysaccharide)/100 g) or a higher fibre diet (13.3 g NSP/100 g) for 18 months. Diverticula were identified by postmortem examination. Caecal and colonic contents were weighed and assayed for short chain fatty acids. Collagen solubility in weak acid was measured to give an indication of the nature and amount of crosslinks in the collagen of the bowel wall. RESULTS--The incidence of colonic diverticula was greater (42.1% fibre deficient rats; 0% higher fibre rats). Colonic collagen solubility index in fibre deficient rats was significantly lower than higher fibre diet fed rats (p &lt; 0.001 in all four sections of the large bowel). Rats with diverticula had the lowest solubility index (p &lt; 0.001 in all four sections of the large bowel). Higher fibre diet rats had increased caecal and colonic contents, caecal and colonic tissue wet weights, and greater caecal short chain fatty acids. Fibre deficient diet fed rats had more pathological abnormalities. CONCLUSIONS--This animal model permits a study of the relation between collagen crosslinkage and the development of colonic diverticulosis. A higher fibre diet protects against collagen crosslinking and this is related to a decreased incidence of diverticula.
Deficiencies in Chfr and Mlh1 synergistically enhance tumor susceptibility in mice
Authors: Zheng Fu, Kevin Regan, Lizhi Zhang, Michael H. Muders, Stephen N. Thibodeau, Amy French, Yanhong Wu, Scott H. Kaufmann, Wilma L. Lingle, Junjie Chen, Donald J. Tindall
Journal: Journal of Clinical Investigation (2009)

Genetic instability, which leads to an accumulation of various genetic abnormalities, has been considered an essential component of the human neoplasic transformation process. However, the molecular basis of genomic instability during tumorigenesis remains incompletely understood. Growing evidence indicates that checkpoint with forkhead and ring finger domains (CHFR), a recently identified mitotic checkpoint protein, plays an important role in maintaining chromosome integrity and functions as a tumor suppressor. In this study, we used high-throughput technology to conduct gene expression profiling of human colon cancers and found that loss of CHFR expression frequently occurred in colon cancers with high microsatellite instability (MSI-H). Downregulation of CHFR expression was closely associated with overexpression of Aurora A, an important mitotic kinase. Mice with deficiencies in both Chfr and Mlh1 (the gene that encodes the DNA mismatch-repair protein Mlh1) displayed dramatically higher incidence of spontaneous tumors relative to mice deficient for only one of these genes. These results suggest that defects in both Chfr and Mlh1 synergistically increase predisposition to tumorigenesis.
An Assessment of the Model of Concentration Addition for Predicting the Estrogenic Activity of Chemical Mixtures in Wastewater Treatment Works Effluents
Authors: Karen L. Thorpe, Melanie Gross-Sorokin, Ian Johnson, Geoff Brighty, Charles R. Tyler
Journal: Environmental Health Perspectives (2005)

The effects of simple mixtures of chemicals, with similar mechanisms of action, can be predicted using the concentration addition model (CA). The ability of this model to predict the estrogenic effects of more complex mixtures such as effluent discharges, however, has yet to be established. Effluents from 43 U.K. wastewater treatment works were analyzed for the presence of the principal estrogenic chemical contaminants, estradiol, estrone, ethinylestradiol, and nonylphenol. The measured concentrations were used to predict the estrogenic activity of each effluent, employing the model of CA, based on the relative potencies of the individual chemicals in an in vitro recombinant yeast estrogen screen (rYES) and a short-term (14-day) in vivo rainbow trout vitellogenin induction assay. Based on the measured concentrations of the four chemicals in the effluents and their relative potencies in each assay, the calculated in vitro and in vivo responses compared well and ranged between 3.5 and 87 ng/L of estradiol equivalents (E2 EQ) for the different effluents. In the rYES, however, the measured E2 EQ concentrations in the effluents ranged between 0.65 and 43 ng E2 EQ/L, and they varied against those predicted by the CA model. Deviations in the estimation of the estrogenic potency of the effluents by the CA model, compared with the measured responses in the rYES, are likely to have resulted from inaccuracies associated with the measurement of the chemicals in the extracts derived from the complex effluents. Such deviations could also result as a consequence of interactions between chemicals present in the extracts that disrupted the activation of the estrogen response elements in the rYES. E2 EQ concentrations derived from the vitellogenic response in fathead minnows exposed to a series of effluent dilutions were highly comparable with the E2 EQ concentrations derived from assessments of the estrogenic potency of these dilutions in the rYES. Together these data support the use of bioassays for determining the estrogenic potency of WwTW effluents, and they highlight the associated problems for modeling approaches that are reliant on measured concentrations of estrogenic chemicals.
Troubles with Tuberculosis Prevention
Authors: Eric J. Rubin
Journal: New England Journal of Medicine (2014)

The prevention of tuberculosis requires multiple tools. Since persons with active disease are the primary mechanism for transmission, treatment of this population is probably the most critical intervention. However, dealing with the very large number of persons with latent tuberculosis, a huge reservoir of potential reactivation, is more problematic. The primary method for preventing disease in this population has been treatment with isoniazid, which is often referred to as secondary prophylaxis. Preventing the development of active tuberculosis with isoniazid monotherapy may work by blocking the reactivation of latent tuberculosis, by treating early infection with a low bacillus burden, or by . . .
Capture of influenza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes
Authors: Santiago F Gonzalez, Veronika Lukacs-Kornek, Michael P Kuligowski, Lisa A Pitcher, Søren E Degn, Young-A Kim, Mary J Cloninger, Luisa Martinez-Pomares, Siamon Gordon, Shannon J Turley, Michael C Carroll
Journal: Nature Immunology (2010)
SERUM SENSITIZATION RESULTING FROM DIPHTHERIA TOXIN-ANTITOXIN ADMINISTRATION
Authors: CHESTER A. STEWART
Journal: JAMA (1927)

Following the initial administration of serum (foreign protein) to patients, particularly when used in considerable amounts, reactions not infrequently occur which are described as serum sickness. These reactions develop most commonly from six to seven or more days following the administration of the foreign protein, and rarely appear earlier than the fifth day.<sup>1</sup>In persons who have been sensitized to serum by its administration at some previous time, the general reactions observed following the second injection of the same foreign protein often differ from ordinary serum sickness, particularly in their more prompt appearance and in their greater severity. The general reactions in serum sensitized patients may be divided into three groups with reference to the time of the onset of symptoms; namely, immediate reactions (those appearing immediately or within a few hours after the serum is injected), accelerated reactions (those appearing from one to three days after injection) and
Methadone Poisoning in a Child
Authors: S. G. Ratcliffe
Journal: BMJ (1963)

MEDICAL JOURNALosteitis and periostitis occurring out of a total of 18,840 cases of typhoid fever-an incidence of 0.82% ; and Webb-Johnson (1917) reported details of 1,118 cases, of which four had osteomyelitis-an incidence of 0.4%.Recent interest has centred on cases of osteomyelitis due to salmonellae other than Salm.typhi and on the relationship between salmonella osteomyelitis and sickle- cell anaemia (De Torregrosa et al., 1960).Recent reports of osteomyelitis due to Salm.typhi have been of isolated cases, and we have found six cases reported in the literature since 1926.
Sharing electronic health records
Authors: Derek F H Pheby
Journal: BMJ (2004)

Editor-The Data Protection Act 1998 does not prohibit the processing of personal information for medical research purposes.Indeed, it is clear from section 33 of the act that such processing is expressly permitted.If it were otherwise, then the act would be in direct conflict with the core aims of the laws that underpin it-namely, the Council of Europe Convention of 1981 and the European Union Directive of 1995.These laws seek to facilitate data processing activities, primarily "free flows" of information, rather than suppress data processing.The problems to which Peto et al refer in their editorial on data protection, informed consent, and research are not Data Protection Act problems but, rather, problems caused by ignorance and misunderstanding. 1 With basic training on the key mechanisms of the act the problems of which the authors complain can be easily overcome.Training need not be an expensive task either.Legal compliance can be achieved at comparatively modest cost.There are two additional points of note.Firstly, the Data Protection Act regulates the processing of personal information relating to living individuals.Thus, research following death is not regulated.Secondly, the act and case law make clear that information will not be "personal data" if it does not identify a living person or if it does not have the individual as its focus or is not significantly biographical.So, if medical researchers do not actually need or seek identification information the act should not be engaged.
Plague: Past, Present, and Future
Authors: Nils Chr Stenseth, Bakyt B Atshabar, Mike Begon, Steven R Belmain, Eric Bertherat, Elisabeth Carniel, Kenneth L Gage, Herwig Leirs, Lila Rahalison
Journal: PLoS Medicine (2008)

The authors argue that plague should be taken much more seriously by the international health community.
Double-Filtration Plasmapheresis for Hypertriglyceridemia
Authors: Renato Candrina
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Recent reports describe the usefulness of plasmapheresis in the acute management of severe type V hyperlipoproteinemia.<sup>1,2</sup>This procedure is usually performed using a continuous-flow centrifugation device that separates plasma from blood cells, and discarded plasma is substituted with either fresh-frozen or stored plasma, albumin, or other plasma derivatives. We also have found useful in the management of severe hypertriglyceridemia double-filtration plasmapheresis, a technique that has found application in Japan<sup>3</sup>for selected cases of familial hypercholesterolemia.<sup>4</sup> <h3>Report of a Case.—</h3> A 61-year-old physician with long-standing non—insulin-dependent diabetes mellitus (poorly controlled by diet and the use of oral agents), obesity (body mass index, 29.5 kg/m<sup>2</sup>), and mixed hyperlipidemia was admitted for severe dyspnea and chest pain. A complex metabolic derangement was documented, with fasting hyperglycemia (glucose level, 13.9 mmol/L), glycosuria, an elevated glycosylated hemoglobin level (9.6%; normal range, 3% to 6%), and fasting chylomicronemia
Cyclooxygenase-2 Expression and Role of Vasoconstrictor Prostanoids in Small Mesenteric Arteries From Patients With Crohn’s Disease
Authors: Antonia Tabernero, Jean-Marie Reimund, Sylvette Chasserot, Christian Dominique Muller, Ramaroson Andriantsitohaina
Journal: Circulation (2003)

The present study investigates the vascular reactivity and the involvement of nitric oxide and prostanoids in regulating vasoconstriction of small mesenteric arteries from patients with Crohn's disease (CD) to understand the vascular component of this pathology.An increased production of proinflammatory cytokines (tumor necrosis factor-alpha and interleukins 1beta, 6, and 8) has been observed in biopsy specimens of inflammatory intestinal mucosa. However, contractile responses of small mesenteric arteries from CD patients in response to norepinephrine were not changed ex vivo when compared with controls. Exposure to either the nitric oxide synthase inhibitor N(G)-nitro-L-arginine or the cyclooxygenase (COX) inhibitor indomethacin did not modify contractions induced by norepinephrine in either control or CD patients. However, in the latter, the specific COX-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide significantly attenuated norepinephrine-induced vasoconstriction. Furthermore, immunohistochemical analysis showed marked COX-2 expression in the whole arterial wall of vessels from CD patients. Vessels from control patients exhibited weak COX-2 staining in the adventitial and endothelial layers only.The above results provide direct evidence for COX-2 expression in small mesenteric arteries from CD patients. They also shed new light on the involvement of vasoconstrictor metabolites of COX in regulating contraction of these arteries. Of particular interest is the balance between vasoconstrictor products from COX-2 and unidentified vasodilatory products that maintained vascular reactivity in a physiological range despite an increase of circulatory cytokines in patients with CD.
Dexamethasone Arterializes Venous Endothelial Cells by Inducing Mitogen-Activated Protein Kinase Phosphatase-1
Authors: Mustafa Zakkar, Le Anh Luong, Hera Chaudhury, Oeyvind Ruud, Prakash P. Punjabi, Jon R. Anderson, John W. Mullholand, Anne T. Clements, Rob Krams, Nicholas Foin, Thanos Athanasiou, Edward L.S. Leen, Justin C. Mason, Dorian O. Haskard, Paul C. Evans
Journal: Circulation (2011)

Vein grafting in coronary artery surgery is complicated by a high restenosis rate resulting from the development of vascular inflammation, intimal hyperplasia, and accelerated atherosclerosis. In contrast, arterial grafts are relatively resistant to these processes. Vascular inflammation is regulated by signaling intermediaries, including p38 mitogen-activated protein (MAP) kinase, that trigger endothelial cell (EC) expression of chemokines (eg, interleukin-8, monocyte chemotactic protein-1) and other proinflammatory molecules. Here, we have tested the hypothesis that p38 MAP kinase activation in response to arterial shear stress (flow) may occur more readily in venous ECs, leading to greater proinflammatory activation.Comparative reverse-transcriptase polymerase chain reaction and Western blotting revealed that arterial shear stress induced p38-dependent expression of monocyte chemotactic protein-1 and interleukin-8 in porcine jugular vein ECs. In contrast, porcine aortic ECs were protected from shear stress-induced expression of p38-dependent chemokines as a result of rapid induction of MAP kinase phosphatase-1. However, we observed with both cultured porcine jugular vein ECs and perfused veins that venous ECs can be protected by brief treatment with dexamethasone, which induced MAP kinase phosphatase-1 to suppress proinflammatory activation.Arterial but not venous ECs are protected from proinflammatory activation in response to short-term exposure to high shear stress by the induction of MAP kinase phosphatase-1. Dexamethasone pretreatment arterializes venous ECs by inducing MAP kinase phosphatase-1 and may protect veins from inflammation.
What is this thing called pain?
Authors: Clifford J. Woolf
Journal: Journal of Clinical Investigation (2010)

To paraphrase Cole Porter’s famous 1926 song, “What is this thing called pain? This funny thing called pain, just who can solve its mystery?” Pain, like love, is all consuming: when you have it, not much else matters, and there is nothing you can do about it. Unlike love, however, we are actually beginning to tease apart the mystery of pain. The substantial progress made over the last decade in revealing the genes, molecules, cells, and circuits that determine the sensation of pain offers new opportunities to manage it, as revealed in this Review series by some of the foremost experts in the field.
DIFFUSE PNEUMOCOCCAL PERITONITIS IN A BOY: POST-OPERATIVE PARALYTIC ILEUS TREATED BY ANTI-GAS-GANGRENE SERUM: EMPYEMA: RECOVERY
Authors: B. S. Simpson
Journal: BMJ (1929)

OI b)lood pressure.We tested tlhis on ourselves below ground in " dull ail,'' and in one section wlhieli lhad been aban- donied oni account of bad ventilation.The differences noted were: slight slowinig of the respiration (16 as compared with 18 above grouniid), anid slight inecrease in plulse rate (84 and 72); it was iiot p)ossible to take a blood pressure readiingr tlhereo as the liglht was so poor.The large aimiouint of CO., in miiille air r-equires somne xJ)laliationl.There is, of course, no0 conspliption of CO2 uili(le-rgrouniid; on the contrary, it is beimg produced con- staiftly.The amounit preseiit is only to a very slight d,rlree due t) resl)iration of ii-men aind ponics anid the l,iollin,g of oil lamiips.It is almiiost entirely d(ue to the oxidizationi of w%ood and of the exposed (eirfaees of the (0J1,toethier withi the gas actuailly 1W;ated froim tlho col! its-e!f.The ethlehr ob'viOIs abnorima1l, fal( toi in thie cond(lition1s of work un''errotrn(i in a(l(litiin to tle comi)osition of the inspired air is the absence of dTay-light.-It is evidclet that ill wsin-ter, at least, many iners el$S(loniiiee suiligit or-even day-light.The iipoi-tanc of this is ol) 11o0v beilng fully ogii s(el, hut at prv,-sent we are iiot p)repr)ll'edi to assess its .sigwnificance in the sulb)ject inudor inlqu1iry.We lhave, 1lowevel, been able to trace a plrogressive tbickening of the arteries witlh tlle lenIigti of timiie (luiligii + which tile ciie xvorked undergrouiid ; this is sliowni in Table VIII.TABLE VIII.