tbuckley/cabot-search huggingface dataset:
Biochemical Nature and Cellular Distribution of the Paired Immunoglobulin-like Receptors, PIR-A and PIR-B
Authors: Hiromi Kubagawa, Ching-Cheng Chen, None Le Hong Ho, Toshihide Shimada, Lanier Gartland, Charles Mashburn, Takahiro Uehara, Jeffrey V. Ravetch, Max D. Cooper
Journal: The Journal of Experimental Medicine (1999)

PIR-A and PIR-B, paired immunoglobulin-like receptors encoded, respectively, by multiple Pira genes and a single Pirb gene in mice, are relatives of the human natural killer (NK) and Fc receptors. Monoclonal and polyclonal antibodies produced against a recombinant PIR protein identified cell surface glycoproteins of approximately 85 and approximately 120 kD on B cells, granulocytes, and macrophages. A disulfide-linked homodimer associated with the cell surface PIR molecules was identified as the Fc receptor common gamma (FcRgammac) chain. Whereas PIR-B fibroblast transfectants expressed cell surface molecules of approximately 120 kD, PIR-A transfectants expressed the approximately 85-kD molecules exclusively intracellularly; PIR-A and FcRgammac cotransfectants expressed the PIR-A/ FcRgammac complex on their cell surface. Correspondingly, PIR-B was normally expressed on the cell surface of splenocytes from FcRgammac-/- mice whereas PIR-A was not. Cell surface levels of PIR molecules on myeloid and B lineage cells increased with cellular differentiation and activation. Dendritic cells, monocytes/macrophages, and mast cells expressed the PIR molecules in varying levels, but T cells and NK cells did not. These experiments define the coordinate cellular expression of PIR-B, an inhibitory receptor, and PIR-A, an activating receptor; demonstrate the requirement of FcRgammac chain association for cell surface PIR-A expression; and suggest that the level of FcRgammac chain expression could differentially affect the PIR-A/PIR-B equilibrium in different cell lineages.
P1079 LAMIVUDINE (LAM) TREATMENT AND OUTCOME IN A SINGLE CENTRE COHORT OF PREGNANT WOMEN WITH HIGH HEPATITIS B VIRAL LOADS
Authors: J.S. Lambert, V. Jackson, W. Ferguson, M. Lawless, M. Eogan, S. Coughlan, J. Connell, U. Nusgen, B. Kelleher
Journal: Journal of Hepatology (2014)
Prognostic Value of Lead aVR in Patients With a First Non–ST-Segment Elevation Acute Myocardial Infarction
Authors: José A. Barrabés, Jaume Figueras, Cristina Moure, Josefa Cortadellas, Jordi Soler-Soler
Journal: Circulation (2003)

ST-segment elevation in lead aVR has been associated with severe coronary artery lesions in patients with acute coronary syndromes, but the prognostic significance of this finding is unknown.We analyzed the initial ECG in 775 consecutive patients admitted to our center with a first acute myocardial infarction without ST-segment elevation in leads other than aVR or V1. The rates of in-hospital death in patients without (n=525) and with 0.05 to 0.1 mV (n=116) or > or =0.1 mV (n=134) of ST-segment elevation in lead aVR were 1.3%, 8.6%, and 19.4%, respectively (P<0.001). After adjustment for the baseline clinical predictors and for ST-segment depression on admission, the odds ratios for death in the last 2 groups were, respectively, 4.2 (95% CI, 1.5 to 12.2) and 6.6 (95% CI, 2.5 to 17.6). The rates of recurrent ischemic events and heart failure during hospital stay also increased in a stepwise fashion among the groups, whereas creatine kinase-MB levels were similar. Among the 437 patients that were catheterized within 6 months, the prevalence of left main or 3-vessel coronary artery disease in the 3 groups was 22.0%, 42.6%, and 66.3%, respectively (P<0.001).Lead aVR contains important short-term prognostic information in patients with a first non-ST-segment elevation acute myocardial infarction. Because the poorer outcome predicted by ST-segment elevation in lead aVR seems to be related to a more severe coronary artery disease, an early invasive approach might be especially beneficial in patients presenting with this finding.
Assessment of Fibrosis by Transient Elastography Compared With Liver Biopsy and Morphometry in Chronic Liver Diseases
Authors: Grace Lai–Hung Wong, Vincent Wai–Sun Wong, Paul Cheung–Lung Choi, Anthony Wing–Hung Chan, Richard Hoi–Leong Chum, Henry Kai–Wing Chan, Kenneth Ka–Ki Lau, Angel Mei–Ling Chim, Karen Ka–Lam Yiu, Francis Ka–Leung Chan, Joseph Jao–Yao Sung, Henry Lik–Yuen Chan
Journal: Clinical Gastroenterology and Hepatology (2008)
Parental Occurrence of Premature Cardiovascular Disease Predicts Increased Coronary Artery and Abdominal Aortic Calcification in the Framingham Offspring and Third Generation Cohorts
Authors: Nisha I. Parikh, Shih-Jen Hwang, Martin G. Larson, L. Adrienne Cupples, Caroline S. Fox, Emily S. Manders, Joanne M. Murabito, Joseph M. Massaro, Udo Hoffmann, Christopher J. O’Donnell
Journal: Circulation (2007)

Background— Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease (CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community. Methods and Results— We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study. Subjects included 797 Framingham Offspring (mean age, 63 years; 56% women) and 1238 Third Generation (Gen3) (mean age, 46 years; 47% women) participants free of CVD. Generalized estimating equations adjusted for major CVD risk factors were used to relate validated parental premature CVD and CHD to CAC and AAC, defined by &gt;90th percentile age- and sex-specific cut points from a healthy subsample. Parental premature CVD was associated with CAC among Gen3 (odds ratio=2.17 [1.41 to 3.33]; P &lt;0.001) and nonsignificantly among Offspring (odds ratio=1.42 [0.91 to 2.22]; P =0.12). Parental premature CHD was associated with CAC among Gen3 (odds ratio=2.22 [1.22 to 4.01]) but not Offspring. Parental premature CVD was not associated with AAC in either cohort. Parental premature CHD was associated with AAC among Gen3 (odds ratio=1.65 [0.99 to 2.75]; P =0.05) but not among Offspring. The magnitude of risk conferred was greater for paternal than maternal premature CVD. Conclusions— Parental premature CVD is associated with CAC, and premature CHD is associated with AAC, after adjustment for risk factors, particularly in younger middle-aged adults. Risk conferred by parental premature CVD on vascular calcification may be mediated through novel mechanisms not accounted for by classic CVD risk factors known to cause atherosclerosis.
Histopathological correlation supports the use of x-rays in the diagnosis of hand osteoarthritis
Authors: Ilse-Gerlinde Sunk, Love Amoyo-Minar, Birgit Niederreiter, Afschin Soleiman, Franz Kainberger, Josef S Smolen, Klaus Bobacz
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To correlate histopathological and radiographic features of distal and proximal interphalangeal (DIP and PIP) joints in order to test whether the use of an x-ray examination would be beneficial to the classification/diagnosis process of hand osteoarthritis (OA). <h3>Methods</h3> DIP and PIP joints were obtained from post mortem specimens (n=40). Plain x-rays of the DIP and PIP joints were taken and radiographic OA was determined by the Kellgren and Lawrence classification. Individual radiographic features were scored according to the method described by Altman. Joint samples were prepared for histological analysis; cartilage damage was graded according to the Mankin scoring system. Spearman9s correlation was applied to examine the relationship between histological and radiographical changes. Differences between groups (bony swelling vs no bony swelling) were determined by Student t test. <h3>Results</h3> A highly significant correlation was found between histological (Mankin score) and radiographic (Kellgren/Lawrence score) changes in the investigated DIP (r<sub>s</sub>=0.87, p&lt;0.0001) and PIP (r<sub>s</sub>=0.79, p&lt;0.0001) joints. A subgroup of patients (37.5% for DIP and 18.8% for PIP joints) showed advanced radiographic changes (Kellgren/Lawrence score ≥2) in joints without clinical bony swelling. Histologically, the mean Mankin scores accounted for 11±1.66 for DIP and 9.67±2.4 for PIP joints. <h3>Conclusion</h3> On the basis of histopathological changes of DIP and PIP joints, this investigation demonstrates the validity of x-ray examinations and supports the use of plain radiography in the diagnosis of hand OA and in the classification of hand OA in clinical trials.
PLEIOTROPIC EFFECTS OF STATINS
Authors: James K. Liao, Ulrich Laufs
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, recent studies indicate that some of the cholesterol-independent or "pleiotropic" effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.
Risk of Birth Abnormalities in the Offspring of Men With a History of Cancer: A Cohort Study Using Danish and Swedish National Registries
Authors: O. Stahl, H. A. Boyd, A. Giwercman, M. Lindholm, A. Jensen, S. Kruger Kjaer, H. Anderson, E. Cavallin-Stahl, L. Rylander
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundThe potential mutagenic effects of cancer therapies and the growing number of young male cancer survivors have given rise to concern about the health of their offspring.
Gastric Dysplasia and Gastric Cancer: Helicobacter pylori, Serum Vitamin C, and Other Risk Factors
Authors: W.-c. You
Journal: JNCI Journal of the National Cancer Institute (2000)

Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer.Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided.The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol.H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.
CHANGES PRODUCED IN MOUSE PLASMA PROTEINS BY ACUTE BACTERIAL INFECTIONS
Authors: Curtis A. Williams, Courtney T. Wemyss
Journal: The Journal of Experimental Medicine (1961)

The immunoelectrophoretic patterns of plasma proteins from mice are altered significantly by acute infections. Some proteins are dissociated into two or more components, some showed striking increase in plasma concentration, others are depleted, and certain ones appear which are undetectable in normal samples. beta(1)-C dissociated into two electrophoretic components under a variety of conditions in addition to infections. Endotoxins and killed organisms in vivo, and specific precipitate absorption, heat and aging in vitro produced this change. Endotoxins injected into mice also induced a rise in haptoglobin though not as sharply or predictably as acute infection. Preliminary results with samples from hospital patients with acute diseases are discussed. It was concluded that study of experimental diseases in laboratory animals by these techniques could provide a fruitful basis for the investigation of the plasma protein changes in similar human diseases.
Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.
Authors: C Bossaller, G B Habib, H Yamamoto, C Williams, S Wells, P D Henry
Journal: Journal of Clinical Investigation (1987)

The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.
Translational failure of anti-inflammatory compounds for myocardial infarction: a meta-analysis of large animal models
Authors: Gerardus P. J. van Hout, Sanne J. Jansen of Lorkeers, Kimberly E. Wever, Emily S. Sena, Lisanne H. J. A. Kouwenberg, Wouter W. van Solinge, Malcolm R. Macleod, Pieter A. Doevendans, Gerard Pasterkamp, Steven A. J. Chamuleau, Imo E. Hoefer
Journal: Cardiovascular Research (2015)

AimsNumerous anti-inflammatory drugs have been tested in large animal studies of myocardial infarction (MI). Despite positive results, translation of anti-inflammatory strategies into clinical practice has proved to be difficult. Critical disparities between preclinical and clinical study design that influence efficacy may partly be responsible for this translational failure. The aim of the present systematic review was to better understand which factors underlie the failure of transition towards the clinic.
Toll-Like Receptor 4 Mediates Maladaptive Left Ventricular Remodeling and Impairs Cardiac Function After Myocardial Infarction
Authors: Leo Timmers, Joost P.G. Sluijter, J. Karlijn van Keulen, Imo E. Hoefer, Marcel G.J. Nederhoff, Marie-Jose Goumans, Pieter A. Doevendans, Cees J.A. van Echteld, Jaap A. Joles, Paul H. Quax, Jan J. Piek, Gerard Pasterkamp, Dominique P.V. de Kleijn
Journal: Circulation Research (2007)

Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction. Therapeutic options to prevent LV remodeling are limited, which necessitates the exploration of alternative therapeutic targets. Toll-like receptors (TLRs) serve as pattern recognition receptors within the innate immune system. Activation of TLR4 results in an inflammatory response and is involved in extracellular matrix degradation, both key processes of LV remodeling following myocardial infarction. To establish the role of TLR4 in postinfarct LV remodeling, myocardial infarction was induced in wild-type BALB/c mice and TLR4-defective C3H- Tlr4 LPS−d mice. Without affecting infarct size, TLR4 defectiveness reduced the extent of LV remodeling (end-diastolic volume: 103.7±6.8 μL versus 128.5±5.7 μL; P &lt;0.01) and preserved systolic function (ejection fraction: 28.2±3.1% versus 16.6±1.3%; P &lt;0.01), as assessed by MRI. In the noninfarcted area, interstitial fibrosis, and myocardial hypertrophy were reduced in C3H- Tlr4 LPS−d mice. In the infarcted area, however, collagen density was increased, which was accompanied by fewer macrophages, reduced inflammation regulating cytokine expression levels (interleukin [IL]-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, tumor necrosis factor-α, interferon-γ, granulocyte/macrophage colony-stimulating factor), and reduced matrix metalloproteinase-2 (4684±515 versus 7573±611; P =0.002) and matrix metalloproteinase-9 activity (76.0±14.3 versus 168.0±36.2; P =0.027). These data provide direct evidence for a causal role of TLR4 in postinfarct maladaptive LV remodeling, probably via inflammatory cytokine production and matrix degradation. TLR4 may therefore constitute a novel target in the treatment of ischemic heart failure.
ON THE INHIBITORY INFLUENCE OF EOSIN UPON SPORULATION
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1908)

Sporulation of B. anthracis, B. subtilis, B. cereus, B. ruminatus, B. mesentericus, B. anthracoides and B. megatherium does not take place in an agar medium containing eosin "Gelb" in a concentration exceeding 0.5 per cent. In a concentration of 0.1 per cent. most of these bacteria fail to produce spores. The greatest sensitiveness is shown by B. cereus and B. mesentericus. In a bouillon medium sporulation is likewise inhibited by eosin, but after a longer time-seven weeks or more-sporulation still occurs where the concentration of the dye equals one-tenth per cent. Sporulation of B. tetani, B. anthracis symptomaticus, B. botulismus, B. oedema maligni, B. enteritidis sporogenes, and B. putrificus does not take place in a medium containing eosin "Gelb" in concentrations exceeding 0.03 per cent. With these organisms, no difference was noted in the final effect, depending on the medium employed. No permanent loss of power to produce spores ensues with the bacteria tested even after long sojourn in the eosinized media. It may be stated that on the whole the inhibitory action of eosin was more pronounced upon the anaerobic than upon the aerobic species of bacteria employed in these experiments.
Microvascular deterioration: implications for reperfusion
Authors: T. FUKUYAMA, B. E SOBEL, R. ROBERTS
Journal: Cardiovascular Research (1984)

Beneficial effects of reperfusion or revascularisation on acute myocardial injury may be restricted to the initial few hours due in part to the development of myocardial haemorrhage and "no-reflow". In the present study, the severity of regional myocardial haemorrhage was assessed with Cr-51-RBC and compared with regional flow in the same areas assessed with labelled microspheres in 51 dogs to determine the temporal profile of reperfusion induced haemorrhage and "no-reflow" in relation to the duration of preceding ischaemia. Reperfusion was initiated after selected intervals of coronary occlusion (1 to 7 h) in 31 dogs, and results compared to those in 14 dogs with persistent occlusion and six dogs with no occlusion. Regions of decreased perfusion were outlined grossly with lissamine dye. Heart rate, blood pressure and left atrial pressures were monitored continuously. Haemorrhage was confirmed by histology. The amount of blood in normal regions of the heart was 3.2 +/- 0.4% of wet weight. In tissue ischaemic for 1 h without reperfusion, it was less, ie, 2.3 +/- 0.7; with occlusion of seven hours, it was reduced even further to 1.3%. in dogs subjected to reperfusion after selected intervals of ischaemia, haemorrhage (6.6 +/- 3.8 ml X 100 g-1) occurred in the endocardium after 3 h of ischaemia but in this epicardium only after 5 h of ischaemia (3.9 +/- 1). Regional flow was normal in the endocardium with reperfusion after 1 h of ischaemia (0.9 +/- 0.2 ml X min-1 X g-1) but decreased by 50% with ischaemia of 7 h prior to reperfusion. Thus, haemorrhage occurred earlier than "no-reflow". Results indicate that the severity of microvascular damage is a function of the duration of the interval of ischaemia prior to reperfusion and that it is evident earliest in the subendocardium. Since haemorrhage preceded "no-reflow" extravasation of blood may contribute to the "no-reflow" phenomenon. Adjunctive measures designed to delay microvascular deterioration may be useful to prolong the interval in which lysis or bypass surgery can be implemented effectively.
TMPRSS2-ERG Fusions Are Strongly Linked to Young Patient Age in Low-grade Prostate Cancer
Authors: Stefan Steurer, Pascale Sophia Mayer, Meike Adam, Antje Krohn, Christina Koop, Daniel Ospina-Klinck, Ali Attarchi Tehrani, Ronald Simon, Pierre Tennstedt, Markus Graefen, Corinna Wittmer, Benedikt Brors, Christoph Plass, Jan Korbel, Joachim Weischenfeldt, Guido Sauter, Hartwig Huland, Maria Christina Tsourlakis, Sarah Minner, Thorsten Schlomm
Journal: European Urology (2014)
Proliferation-dependent HIV-1 infection of monocytes occurs during differentiation into macrophages.
Authors: H Schuitemaker, N A Kootstra, M H Koppelman, S M Bruisten, H G Huisman, M Tersmette, F Miedema
Journal: Journal of Clinical Investigation (1992)

Requirements for the establishment of productive infection with the human immunodeficiency virus type 1 (HIV-1) in primary monocytes were investigated. In vitro, monocytes rendered susceptible for infection after at least a 2-d culture, but when cultured in the presence of differentiation-inducing agent IL-4, accelerated susceptibility was seen. Complete resistance to HIV-1 infection was observed in monocytes that had been treated for 5 d with rIL-4, and comparable results were obtained with other differentiation inducers such as dexamethasone or 1,25(OH)2 vitamin D3 (1,25(OH)2vitD3). The inhibition of productive infection was not caused by downregulation of CD4 expression or HIV-1 transcription, nor by intracellular accumulation of virions. Since treatment with rIL-4, dexamethasone, or 1,25(OH)2vitD3 also resulted in complete inhibition of monocyte proliferation, we studied whether establishment of productive infection in monocytes is proliferation dependent. Irradiation or mitomycin-C treatment within 24 h after inoculation prevented productive HIV-1 infection of monocytes, suggesting a proliferation-dependent step early in the virus replication cycle. Polymerase chain reaction (PCR) analysis revealed the presence of only incomplete proviral DNA species in non-proliferating monocytes, indicating restriction of viral replication at the level of reverse transcription. Thus, in analogy with HIV-1 infection of CD4+ T cells, proliferation of monocytes during differentiation into macrophages is a prerequisite for productive infection with HIV.