tbuckley/cabot-search huggingface dataset:
Coronary artery calcium score prediction of all cause mortality and cardiovascular events in people with type 2 diabetes: systematic review and meta-analysis
Authors: C. K. Kramer, B. Zinman, J. L. Gross, L. H. Canani, T. C. Rodrigues, M. J. Azevedo, R. Retnakaran
Journal: BMJ (2013)

<b>Objective</b> To investigate the association of coronary artery calcium score with all cause mortality and cardiovascular events in people with type 2 diabetes. <b>Design</b> Systematic review and meta-analysis of observational studies. <b>Data sources</b> Studies were identified from Embase, PubMed, and abstracts from the 2011 and 2012 annual meetings of the American Diabetes Association, European Association for the Study of Diabetes, American College of Cardiology, and American Heart Association (2011). <b>Eligibility criteria</b> Prospective studies that evaluated baseline coronary artery calcium score in people with type 2 diabetes and subsequent all cause mortality or cardiovascular events (fatal and non-fatal). <b>Data extraction</b> Two independent reviewers extracted the data. The predictive value of the coronary artery calcium score was assessed by random effects model. <b>Results</b> Eight studies were included (n=6521; 802 events; mean follow-up 5.18 years). The relative risk for all cause mortality or cardiovascular events, or both comparing a total coronary artery calcium score of ≥10 with a score of &lt;10 was 5.47 (95% confidence interval 2.59 to 11.53; I<sup>2</sup>=82.4%, P&lt;0.001). The overall sensitivity of a total coronary artery calcium score of ≥10 for this composite outcome was 94% (95% confidence interval 89% to 96%), with a specificity of 34% (24% to 44%). The positive and negative likelihood ratios were 1.41 (95% confidence interval 1.20 to 1.66) and 0.18 (0.10 to 0.30), respectively. For people with a coronary artery calcium score of &lt;10, the post-test probability of the composite outcome was about 1.8%, representing a 6.8-fold reduction from the pretest probability. Four studies evaluated cardiovascular events as the outcome (n=1805; 351 events). The relative risk for cardiovascular events comparing a total coronary artery calcium score of ≥10 with a score of &lt;10 was 9.22 (2.73 to 31.07; I<sup>2</sup>=76.7%, P=0.005). The positive and negative likelihood ratios were 1.67 (1.30 to 2.17) and 0.11 (0.04 to 0.29), respectively. <b>Conclusion</b> In people with type 2 diabetes, a coronary artery calcium score of ≥10 predicts all cause mortality or cardiovascular events, or both, and cardiovascular events alone, with high sensitivity but low specificity. Clinically, the finding of a coronary artery calcium score of &lt;10 may facilitate risk stratification by enabling the identification of people at low risk within this high risk population.
The evolution of language: Present behavioral evidence for past genetic reprogramming in the human lineage
Authors: Robert B. Eckhardt
Journal: Behavioral and Brain Sciences (2006)

Language and life history can be related functionally through the study of human ontogeny, thus usefully informing our understanding of several unique aspects of the evolution of species. The operational principles outlined by Locke &amp; Bogin (L&amp;B) demonstrate that the present can provide a useful framework for understanding the past.
Analytical subcellular fractionation of cultivated mouse resident peritoneal macrophages
Authors: C Darte, H Beaufay
Journal: The Journal of Experimental Medicine (1983)

Resident peritoneal macrophages of the mouse, cultivated for 3 d, have been studied by quantitative subcellular fractionation using differential centrifugation and density equilibration in linear gradients of sucrose. Density equilibration experiments were carried out on untreated cytoplasmic extracts, on cytoplasmic extracts treated with digitonin or sodium pyrophosphate, and on cytoplasmic extracts derived from cells cultivated for 24 h in the presence of Triton WR-1339. The enzyme distributions obtained distinguished six typical behaviors characteristic of distinct subcellular entities. Acid α-galactosidase and other acid hydrolases displayed the highest average velocity of sedimentation and equilibrium density. Culturing in a medium that contained Triton WR-1339 markedly decreased their density, most likely as a result of Triton WR-1339 accumulation within lysosomes. Cytochrome c oxidase and the sedimentable activity of malate dehydrogenase showed a narrow density distribution centered around 1.17, very similar under all the experimental situations; their rate of sedimentation fell within the range expected for mitochondria. Catalase was particle-bound and exhibited structure-linked latency (80 percent); it was released in soluble and fully active form by digitonin, but this required a much higher concentration than in the case of lysosomal enzymes. Differences relative to all the other enzymes studied suggest the existence of a particular species of organelles, distinctly smaller than mitochondria, and possibly related to peroxisomes. Many enzymes were microsomal in the sense that the specific activities, but not the yields, were greater in microsomes than in other fractions obtained by differential centrifugation. These enzymes were distinguished in three groups by their properties in density equilibration experiments. NAD glycohydrolase, alkaline phosphodiesterase I, and 5'-nucleotidase had low equilibrium densities but became noticeably more dense after addition of digitonin. The other microsomal enzymes were not shifted by digitonin, in particular N-acetylglucosaminyltransferase and galactosyltransferase, which otherwise equilibrated at the same position in the gradient. We assign the digitonin-sensitive enzymes to plasma membranes and possibly to related endomembranes of the cells, and the two glycosyltransferases to elements derived from the Golgi apparatus. Finally, α-glucosidase, sulphatase C, NADH cytochrome c reductase, NADPH cytochrome c reductase, and mannosyltransferase, equilibrated at a relatively high density but were shifted to lower density values after addition of sodium pyrophosphate. These properties support their association with elements derived from the endoplasmic reticulum.
Hyperoxaluria correlates with fat malabsorption in patients with sprue.
Authors: G B McDonald, D L Earnest, W H Admirand
Journal: Gut (1977)

The effect of fat malabsorption on the absorption and renal excretion of dietary oxalate was studied in four patients with sprue and in two patients with dermatitis herpetiformis and sprue-like jejunal histology. Hyperoxaluria was present in all patients with sprue when fat malabsorption was severe. Urinary oxalate excretion decreased in two of the three patients with coeliac sprue when their fat malabsorption had improved after three months of dietary gluten restriction. Neither patient with dermatitis herpetiformis and sprue had steatorrhoea. In these patients, urinary oxalate excretion was always within normal limits. A significant positive linear relationship (y=28.25 +4-84x; r=0-82; P less than 0-01) was demonstrated between faecal fat and urinary oxalate excretion. The results of this study support the concept that severe malabsorption of dietary fat plays a primary causative role in enteric hyperoxaluria.
Paradoxical effects of a synthetic metalloproteinase inhibitor that blocks both p55 and p75 TNF receptor shedding and TNF alpha processing in RA synovial membrane cell cultures.
Authors: L M Williams, D L Gibbons, A Gearing, R N Maini, M Feldmann, F M Brennan
Journal: Journal of Clinical Investigation (1996)

We have previously hypothesized that the pro-inflammatory cytokine TNF alpha has a pivotal role in the pathogenesis of rheumatoid arthritis (RA). It mediates its effects by cross-linking surface p55 TNF receptors (TNF-R), which can be proteolytically cleaved to yield soluble fragments. Upon binding TNF alpha soluble TNF-R (sTNF-R) can inhibit its function. We investigated the enzymatic nature of the proteases involved in TNF-R cleavage, and found that this process is blocked by a synthetic inhibitor of matrix metallo-proteinase activity (MMP), BB-2275. Inhibition of TNF-R cleavage was observed in a number of different cell types, as detected by retention of surface bound TNF receptor and by less sTNF-R released into the cell supernatant. The augmentation of surface TNF-R expression was of biological relevance as TNF alpha-mediated necrosis of human KYM.1D4 rhabdosarcoma cells was enhanced approximately 15-fold in the presence of BB-2275. The addition of BB-2275 to rheumatoid synovial membrane cell cultures totally inhibited MMP activity and also significantly reduced the levels of soluble TNF alpha (P < 0.006), p55 sTNF-R (P < 0.006), and p75 sTNF-R (P < 0.004). Paradoxically, despite the reduction in soluble TNF alpha levels, the production of IL-1 beta, IL-6, and IL-8, cytokines whose production was previously demonstrated to be inhibited by the addition of neutralizing anti-TNF alpha antibody were not down-regulated by BB-2275. These results raise the interesting possibility that a close relationship exits between the enzyme(s) which process membrane-bound TNF alpha, and those involved in surface TNF-R cleavage. Furthermore our observations suggest that hydroxamate inhibitors of MMP activity which block TNF alpha secretion and TNF-R cleavage may not modulate down-stream effects of TNA alpha, and as such suggest that the precise specificity of these compounds will be highly relevant to their clinical efficacy in inflammatory diseases.
Soluble intercellular adhesion molecule‐1 in the bronchoalveolar lavage fluid of normal children exposed to parental cigarette smoke
Authors: J. Grigg, J. Riedler, C.F. Robertson
Journal: European Respiratory Journal (1999)

This study sought to test the hypothesis that normal children exposed to parental cigarette smoke have increased bronchoalveolar lavage (BAL) fluid levels of soluble intercellular adhesion molecule (sICAM)-1. Cells and solutes from the lower airway of normal children were obtained by nonbronchoscopic BAL using three aliquots of 1 mL x kg body weight(-1) normal saline, prior to elective orthopaedic surgery. Children with evidence of recent or ongoing infection, atopic disease, previous history of wheeze, and chronic respiratory symptoms were excluded. Twelve children with parents who smoked (group 1) were paired with 12 age- and weight-matched controls with self-reported nonsmoking parents (group 2). There was no significant difference (group 1 versus 2) in the volume of BAL fluid recovered (median 29.0 versus 28.7 mL), the percentage of alveolar macrophages (92.5 versus 91.8%), neutrophils (1.1 versus 2.1%), lymphocytes (5.3 versus 5.6%) and eosinophils (0 versus 0%), and the total BAL fluid leukocyte concentration (80 versus 61 x 10(3) cells x mL(-1)). BAL fluid albumin concentration was similar between the two groups (0.033 versus 0.020 mg x mL(-1)). sICAM-1 was detected in all BAL fluid samples, and was significantly increased in group 1 (39.2 versus 22.5 ng x mL(-1), p&lt;0.01). It was concluded that exposure of children to parental cigarette smoke is associated with increased soluble intercellular adhesion molecule-1 concentrations in the bronchoalveolar lavage fluid and this may reflect an altered activation of pulmonary immune cells.
Can robots without Hebbian plasticity make good models of adaptive behaviour?
Authors: Jørn Hokland, Beatrix Vereijken
Journal: Behavioral and Brain Sciences (2001)

No. Animals' primary problem is the shaping of movements, guided by and adapting to sensory signals. This requires a narrower class of biorobotic models than that spanned by Webb's dimensions and examples. We claim that all model variables and mechanisms must have real counterparts, input vectors must model known sensor fields, internal state vectors and transformations must model neurophysiological processes, and output vectors must model coordinated muscle signals.
Abstract IA2: The molecular basis of tumor immunogenicity.
Authors: Robert D. Schreiber
Journal: Cancer Research (2013)

Abstract Cancer Immunoediting is the process by which the immune system controls and shapes cancer. We originally envisaged that cancer immunoediting would occur in three phases: Elimination (also known as cancer immunosurveillance, the host protective phase of the process), Equilibrium (the phase in which tumor cells that survive immune elimination remain under immunologic growth control resulting in a state of functional tumor dormancy) and Escape (the phase where clinically apparent tumors emerge because immune sculpting of the tumor cells has produced variants that display either reduced immunogenicity or enhanced immunosuppressive activity). Strong experimental data has now been obtained using mouse models of cancer to demonstrate the existence of each phase of the cancer immunoediting process and compelling clinical data suggests that a similar process may also occur during the evolution of certain types of human cancer. Our efforts now focus on elucidating the molecular and cellular mechanisms that underlie each phase of cancer immunoediting and identifying the critical checkpoints that regulate progression from one phase of the process to the next. This approach has helped identify the nature of antigens seen by immunity in nascent developing cancers and has further shown that immunoselection is a major mechanism of immunoediting. Moreover, we have found that edited tumors can still be controlled by the immune system if natural mechanisms that prevent autoimmunity are suspended. As reported by others, we have confirmed that inhibition of CTLA-4 induces ejection of edited MCA sarcomas. However, we have also found that inhibition of PD-L1 does the same, although by perhaps different mechanisms. These differences will be discussed. Citation Format: Robert D. Schreiber. The molecular basis of tumor immunogenicity. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr IA2.
Acquired Coronary Artery Fistula From Nonpenetrating Chest Injury
Authors: Alan D. Forker
Journal: JAMA (1971)

An anterior myocardial contusion resulted from a nonpenetrating chest injury. A continuous murmur was detected four years later, and a left anterior descending coronary artery to right ventricular fistula was surgically ligated twice, with recurrence of the fistula three months after the initial ligation. Six previous traumatic coronary artery fistulas have been reported, all secondary to penetrating chest trauma.
Cop1 constitutively regulates c-Jun protein stability and functions as a tumor suppressor in mice
Authors: Domenico Migliorini, Sven Bogaerts, Dieter Defever, Rajesh Vyas, Geertrui Denecker, Enrico Radaelli, Aleksandra Zwolinska, Vanessa Depaepe, Tino Hochepied, William C. Skarnes, Jean-Christophe Marine
Journal: Journal of Clinical Investigation (2011)

Biochemical studies have suggested conflicting roles for the E3 ubiquitin ligase constitutive photomorphogenesis protein 1 (Cop1; also known as Rfwd2) in tumorigenesis, providing evidence for both the oncoprotein c-Jun and the tumor suppressor p53 as its targets. Here we present what we believe to be the first in vivo investigation of the role of Cop1 in cancer etiology. Using an innovative genetic approach to generate an allelic series of Cop1, we found that Cop1 hypomorphic mice spontaneously developed malignancy at a high frequency in the first year of life and were highly susceptible to radiation-induced lymphomagenesis. Further analysis revealed that c-Jun was a key physiological target for Cop1 and that Cop1 constitutively kept c-Jun at low levels in vivo and thereby modulated c-Jun/AP-1 transcriptional activity. Importantly, Cop1 deficiency stimulated cell proliferation in a c-Jun–dependent manner. Focal deletions of COP1 were observed at significant frequency across several cancer types, and COP1 loss was determined to be one of the mechanisms leading to c-Jun upregulation in human cancer. We therefore conclude that Cop1 is a tumor suppressor that functions, at least in part, by antagonizing c-Jun oncogenic activity. In the absence of evidence for a genetic interaction between Cop1 and p53, our data strongly argue against the use of Cop1-inhibitory drugs for cancer therapy.
The Beginning of the End of the Beginning in Cancer Genomics
Authors: David P. Steensma
Journal: New England Journal of Medicine (2013)

This is the age of massive genome surveys — at least for a little while longer. Sixty years after Watson and Crick's discovery, and a decade after the completion of the Human Genome Project, large-scale sequencing efforts directed at human disease abound, especially for cancer and rare congenital syndromes.1,2 International research teams supported by public funding agencies such as the National Institutes of Health and by private foundations such as the Wellcome Trust are rapidly enlarging the catalogue of genetic changes associated with neoplasia and other ailments, using ever faster, ever cheaper sequencing methods and heavy-duty bioinformatics.Critics of . . .
Michael Gerard McEntegart
Authors: K. McCarthy
Journal: BMJ (2002)

Former professor of medical microbiology and consultant Royal Hallamshire and Sheffield Children's Hospitals (b Gerrards Cross 1921; q Liverpool 1944; MD, FRCPath), died from complications of diverticulitis and parkinsonism on 19 August 2001.

He served in the Royal Army Medical Corps from 1945 to 1947 in Egypt, Kenya, and Italy. Before being appointed to the Sheffield chair, he held posts as assistant lecturer in bacteriology in Liverpool, deputy director of Liverpool public health laboratory service, and senior lecturer in Aberdeen and Newcastle. Michael was a skilled photographer and woodworker. On his retirement in 1982 he and his wife, Betty, moved to a smallholding and acquired a flock of sheep.
Crystal-associated nephropathy in patients with brushite nephrolithiasis
Authors: Andrew P. Evan, James E. Lingeman, Fredric L. Coe, Youzhi Shao, Joan H. Parks, Sharon B. Bledsoe, Carrie L. Phillips, Stephen Bonsib, Elaine M. Worcester, Andre J. Sommer, Sam C. Kim, William W. Tinmouth, Marc Grynpas
Journal: Kidney International (2005)
Phase 1/2 study to assess the safety, efficacy, and pharmacokinetics of barasertib (AZD1152) in patients with advanced acute myeloid leukemia
Authors: Bob Löwenberg, Petra Muus, Gert Ossenkoppele, Philippe Rousselot, Jean-Yves Cahn, Norbert Ifrah, Giovanni Martinelli, Sergio Amadori, Ellin Berman, Pieter Sonneveld, Mojca Jongen-Lavrencic, Sophie Rigaudeau, Paul Stockman, Alison Goudie, Stefan Faderl, Elias Jabbour, Hagop Kantarjian
Journal: Blood (2011)
AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DOCTOR JOSEPH HERSEY PRATT
Authors: HUMPHRY ROLLESTON
Journal: Annals of Internal Medicine (1937)

Article1 August 1937AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DOCTOR JOSEPH HERSEY PRATTSAMUEL JONES GEE AND HIS FRIENDS*HUMPHRY ROLLESTON, Bt., G.C.V.O., K.C.B.HUMPHRY ROLLESTON, Bt., G.C.V.O., K.C.B.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-2-387 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPerhaps the best way I can join in a tribute to Joseph Hersey Pratt—the clinical physician—is to offer a sketch of another clinical physician, at St. Bartholomew's Hospital, with some sidelights on contemporary medical London when I was a student there half a century ago. The names of great physicians have often been linked by their admirers with recently recognized forms of disease, and also with favourite prescriptions—the least of their achievements. Samuel Jones Gee is an example of this eponymous association. Fifty years ago what is now known as posterior basal meningitis or, as Still showed in 1898, chronic...References BARLOW T: The Annual Presidential Address delivered to The Royal College of Physicians of London, 1912, pp. 18-23, London. Google Scholar BENNETTHUNTERVAUGHAN TIDJM: Quart. Jr. Med., Oxford, 1932, N.S.I. 603-677. Google Scholar GEE SJ: Brit. Med. Jr., 1867, i, 437. Google Scholar GEE SJ: On the coeliac affection, St. Barth. Hosp. Rep., London, 1888, xxiv, 17-20. Google Scholar GEE SJ: Medical Lectures and Aphorisms, London, 1902. Google Scholar GEEBARLOW SJT: On the cervical opisthotonos of infants, St. Barth. Hosp. Rep., London, 1878, xiv, 23-42. Google Scholar HORDER TJ: St. Barth. Hosp. Rep., 1897, xxxii, 29. Google Scholar HORDER TJ: Medical Notes, 1921, H. Frowde, London. Google Scholar LEESBARLOW DBT: System of Medicine (Allbutt), London, 1899, vii, 492. Google Scholar LEGG JW: Recollections of Samuel Gee in 4th Ed. (1915) of Medical Lectures and Aphorisms by Samuel Gee. Google Scholar MOOREO'FARRELLGERAGHTYHAYDENMORIATY HJMJAJMM: Quart. Jr. Med., Oxford, 1936, v, 481. Google Scholar MORGENSEN E: Quart. Jr. Med., Oxford, 1937, vi, 119-141. Google Scholar STILL GF: The bacteriology of the simple posterior basic meningitis of infants, Jr. Path. and Bacteriol., London and Edinburgh, 1898, v. 147-159. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication May 24, 1937. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEFFECT OF FLIGHT ON THE MIDDLE EARSAMUEL GEE 1 August 1937Volume 11, Issue 2Page: 387-399KeywordsMeningitis ePublished: 1 December 2008 Issue Published: 1 August 1937 PDF downloadLoading ...
Breathlessness and Anxiety
Authors: A. K. Zealley, R. C. B. Aitken
Journal: BMJ (1970)

A.C.T.H. release are still circulating for very considerable times after injection of methylprednisolone.Studies on our own patients and observations by Jacombe et al. 1 suggest that after 17-20 days the resting plasma cortisol had returned to within the normal range, presumably because by this time there is little or no circulating exogenous steroid.Nevertheless, in our own study the adrenal response to A.C.T.H. remained suppiessed beyond this time, and even in patients studied for 60 days did not regain its former levels.We therefore considered that this degree of depression of adrenal response represented a recovery phase following the disappearance of exogenous steroid from the plasma.It seems important to re-state the con- clusion which we drew in our paper-that is, that this small degree of-suppression would probably be unimportant if only two doses of methylprednisolone were given.A more prolonged course of treatment though might produce correspondingly greater effects.-Weare, etc.,
Tuberculin: Past, Present, and Future
Authors: Vernon N. Houck
Journal: JAMA (1972)

Major discrepancies between the results obtained with the different tuberculin products labeled 5 TU have been reported<sup>1-3</sup>and are becoming increasingly familiar in recent years. Because of an instability reported in potency of reconstituted tableted purified protein derivative (PPD) tuberculins, the Division of Biologics Standards (DBS), National Institutes of Health, called together an ad hoc advisory committee on Jan 18, 1972 to make recommendations to DBS regarding tuberculin testing materials. Information relative to the problem appearing in the scientific literature, data accumulated by various groups doing comparative skin testing, and data developed by DBS, the Center for Disease Control, and the various manufacturers of tuberculin were reviewed. On the basis of the available information, the following recommendations were made: That the tableted forms of PPD tuberculin be replaced as soon as possible (but not to exceed 12 months) with liquid PPD tuberculin containing polysorbate (Tween) or a product