tbuckley/cabot-search huggingface dataset:
Isolation of the receptor for IgG from a human monocyte cell line (U937) and from human peripheral blood monocytes.
Authors: C L Anderson
Journal: The Journal of Experimental Medicine (1982)

The Fc receptors for IgG from a human monocyte line (U937) and from highly purified human peripheral blood monocytes were solubilized, purified, and partially characterized. Both sources of cells gave indistinguishable results. Two molecules (or sets of molecules), one of about 72,000 mol wt and the other of 40,000-43,000 mol wt were discerned on autoradiograms of sodium dodecyl sulfate (SDS)-polyacrylamide gels analyzing acid eluates from Sepharose-IgG columns over which detergent lysates of radioiodinated cells had been passed. The larger of the two molecules, p72, accounted for greater than or equal to 90% of the radioactivity. This component was noted to be heterodisperse both by size on SDS gels and by charge on isoelectric focusing gels. The charge heterogeneity, being virtually eliminated by neuraminidase and tunicamycin, was probably due to variable glycosylation. Several lines of evidence indicated that p72 is probably all or part of the Fc receptor: (a) radiolabeling of this molecule using chloroglycouril was blocked by IgG of the Fc receptor; (b) in soluble form this molecule expressed ligand specificity identical to the in situ receptor; (c) the molecule was not recovered from affinity adsorbants bearing proteins that do not bind to the Fc receptors, nor (d) from a human T cell line that does not bear Fc receptors. The smaller of the two molecules isolated, p40-43, is at least in part actin. Its relationship to p72 is not understood.
Lipoproteins and their subfractions in psoriatic arthritis: identification of an atherogenic profile with active joint disease
Authors: S M Jones
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> (<i>a</i>) To characterise the lipid profile in psoriatic arthritis and investigate whether there are similarities to the dyslipoproteinaemia reported in rheumatoid arthritis and other inflammatory forms of joint disease; (<i>b</i>) to investigate whether there is an atherogenic lipid profile in psoriatic arthritis, which may have a bearing on mortality. <h3>METHODS</h3> Fasting lipids, lipoproteins, and their subfractions were measured in 50 patients with psoriatic arthritis and their age and sex matched controls. <h3>RESULTS</h3> High density lipoprotein cholesterol (HDL cholesterol) and its third subfraction, HDL<sub>3</sub> cholesterol, were significantly reduced and the most dense subfraction of low density lipoprotein (LDL), LDL<sub>3</sub>, was significantly increased in the patients with psoriatic arthritis. Twenty patients with active synovitis had significantly lower total cholesterol, LDL cholesterol, and HDL<sub>3</sub> cholesterol than their controls. 25% of the patients with psoriatic arthritis had raised Lp(a) lipoprotein levels (&gt;300 mg/l) compared with 19% of controls, but this was not statistically significant. <h3>CONCLUSION</h3> Raised levels of LDL<sub>3</sub> and low levels of HDL cholesterol are associated with coronary artery disease. Such an atherogenic profile in a chronic inflammatory form of arthritis is reported, which may be associated with accelerated mortality.
Variation in ICOSLG influences Crohn's disease susceptibility
Authors: P. Henderson, J. van Limbergen, N. H. Anderson, E. R. Nimmo, R. K. Russell, J. Satsangi, D. C. Wilson
Journal: Gut (2011)

Recent genome-wide association studies have identified more than 70 loci which confer susceptibility to Crohn's disease (CD).1 However, the critical coding regions within most of these loci are largely unidentified and it is therefore important that further work is carried out to robustly identify the candidate genes to guide future deep sequencing studies. A locus on chromosome 21q22 harbouring several genes including inducible T cell costimulator ( ICOSLG ), autoimmune regulator ( AIRE ) and periodic tryptophan protein 2 homologue ( PWP2 ) has been shown to influence susceptibility to both adult and paediatric CD and ulcerative colitis (UC).1 2 The protein encoded by ICOSLG is intimately involved in the proliferation and differentiation of T lymphocytes (through binding with inducible T-cell costimulator (ICOS)), especially with regard to the balance between regulatory and Th17 subsets.

We read with interest the …
Welby and 23 other faith leaders declare opposition to assisted dying bill
Authors: Clare Dyer
Journal: BMJ (2015)

Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-β1 and PGE<sub>2</sub>, which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-κB ligand, receptor activator of NF-κB, ICAM-1, and CD44. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-β1 and PGE<sub>2</sub> and decreased the expression of receptor activator for NF-κB ligand, receptor activator of NF-κB, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-β1 together with PGE<sub>2</sub> significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-β1 and PGE<sub>2</sub> release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.
Fertility of Patients With Schizophrenia, Their Siblings, and the General Population: A Cohort Study From 1950 to 1959 in Finland
Authors: Jari Haukka, Jaana Suvisaari, Jouko Lönnqvist
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: Genetic factors are the most important risk factors for schizophrenia. However, despite the fact that patients with schizophrenia have significantly fewer offspring than the general population, schizophrenia persists. The authors investigated whether the siblings of patients with schizophrenia produce more offspring, thereby compensating for the low fertility of the affected individuals. METHOD: From all 870,093 individuals born in Finland from 1950 to 1959, the authors determined how many had schizophrenia or were siblings of schizophrenia patients and how many offspring they had. The population data were obtained from the Population Register Center of Finland, and the National Hospital Discharge Register was used to identify all persons who had been hospitalized because of schizophrenia. Appropriate regression models were used to model age at the birth of the first child, number of children, and proportion of males among offspring. RESULTS: Of the total population, 1.3% were patients with schizophrenia, and 2.8% were their siblings. The mean number of offspring among female siblings was slightly but significantly higher than among women in the general population (1.89 versus 1.83), while the opposite was true for the male siblings (1.57 versus 1.65 among men in the general population). The mean number of offspring among patients with schizophrenia was 0.83 for women and 0.44 for men. CONCLUSIONS: Lower than average fertility among patients with schizophrenia is not compensated for by higher fertility among their siblings. Thus, the persistence of schizophrenia in the general population is not explained by this simple evolutionary mechanism.
Pathologic Anatomy and Patterns of Occurrence of Hepatic Neoplasms, Putative Preneoplastic Lesions, and Other Idiopathic Hepatic Conditions in English Sole (&lt;italic&gt;Parophrys vetulus&lt;/italic&gt;) From Puget Sound, Washington&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Mark S. Myers, Linda D. Rhodes, Bruce B. McCain
Journal: JNCI Journal of the National Cancer Institute (1987)

A comprehensive description of the histopathologic characteristics of a spectrum of idiopathic lesions in feral English sole (Parophrys vetulus), a bottom-dwelling flatfish, from Puget Sound, Washington State, is presented. Among these lesions are unique degenerative conditions, regeneration, storage disorders, foci of hepatocellular alteration (putative preneoplastic lesions), hepatocellular and biliary neoplasms, and nonneoplastic proliferative conditions, all of which morphologically resemble the lesions induced by various hepatocarcinogens-hepatotoxins in experimental exposures of fish and/or rodents. Results from a statistical analysis of the patterns of co-occurrence of these lesions in English sole are consistent with the concept, developed from experimental studies of liver carcinogenesis in rodents, that there are morphologically identifiable steps representing progression toward hepatic neoplasms. This is the first study in which it has been possible to demonstrate a close morphological congruity between a set of idiopathic hepatic lesions in any feral population and an established series of hepatic lesions inducible in rodents by certain hepatocarcinogens under laboratory conditions. Since sediments from the habitats occupied by the fish in this study have been shown to contain multiple hepatocarcinogens, the findings strengthen cumulative evidence that English sole are useful as indicators of exposure to hepatocarcinogens in aquatic environments.
Treatment of childhood Hodgkin’s disease with COPP or COPP-ABV (hybrid) without radiotherapy in Nicaragua
Authors: F. Baez, E. Ocampo, V. Conter, A. Flores, T. Gutierrez, A. Malta, C. Pacheco, R. Palacios, A. Biondi, L. Riva, A. Sala, D. Silvestri, F. Cavalli, C. Sessa, M. Casanova, G. Masera
Journal: Annals of Oncology (1997)
Helicobacter pylori upregulates matrilysin (MMP-7) in epithelial cells in vivo and in vitro in a Cag dependent manner
Authors: J R Bebb
Journal: Gut (2003)

<b>Background and aims:</b> Matrix metalloproteinase-7 (MMP-7) is important in normal and pathological remodelling of epithelial-matrix interactions, and is upregulated in gastric cancer. <i>Helicobacter pylori</i> infection is the first stage in gastric carcinogenesis, and therefore our aim was to determine if <i>H pylori</i> upregulated gastric MMP-7 expression and if this was affected by strain virulence. <b>Methods:</b> We took gastric biopsy specimens at endoscopy from <i>H pylori</i> infected (n = 17) and uninfected (n = 18) patients and assessed MMP-7 expression by ELISA, real time polymerase chain reaction (PCR), and immunohistochemistry (concentrating on epithelial cells in the proliferative zone). We PCR typed <i>H pylori</i> for <i>cagE</i> and <i>vacA</i>. We performed <i>H pylori</i>/cell line coculture studies with wild-type pathogenic and non-pathogenic <i>H pylori</i> strains and with CagE<sup>−</sup> and VacA<sup>−</sup> isogenic mutants. <b>Results:</b> Gastric biopsy specimens from <i>H pylori</i>+ patients expressed higher levels of MMP-7 at the protein and mRNA levels in the antrum and corpus (for example, by ELISA: <i>H pylori</i>+ 0.182 OD units <i>v</i><i>H pylori</i>− 0.059; p = 0.009 antrum). Epithelial cells from <i>H pylori+</i> patients stained more intensely for MMP-7 than those from uninfected patients, including in the proliferative zone containing pluripotent cells (p&lt;0.03 antrum, p&lt;0.04 body). Upregulation of MMP-7 in epithelial cells was confirmed at the protein and mRNA levels by <i>H pylori</i>/cell line coculture. These experiments also showed that MMP-7 upregulation was dependent on an intact <i>H pylori</i><i>cag</i> pathogenicity island but not on the vacuolating cytotoxin. <b>Conclusion:</b> We speculate that increased expression of MMP-7 in <i>H pylori</i> gastritis may contribute to gastric carcinogenesis.
OX26/CTX-conjugated PEGylated liposome as a dual-targeting gene delivery system for brain glioma
Authors: Pei-jian Yue, Lei He, Shu-wei Qiu, Yi Li, Yi-ji Liao, Xiang-pen Li, Dan Xie, Ying Peng
Journal: Molecular Cancer (2014)

The successful gene delivery into the brain is a major challenge due to the presence of the blood–brain barrier (BBB). In order to transport plasmid DNA across the BBB and target the brain glioma, the PEGylated liposomes (PLs) modified with OX26 and chlorotoxin (CTX) were developed as a dual-targeting gene delivery system, and the therapeutic efficacy of OX26/CTX-PL/pC27 against glioma was evaluated using in vitro and in vivo experimental models. The PEGylated liposome complexes were prepared by the reverse phase evaporation method, and their physicochemical properties were examined. The transfection efficiency, intracellular distribution, in vitro effects of OX26/CTX-PL/pC27 were determined on C6, F98 and HEK293T cell lines. The dual-targeting therapeutic efficacy of OX26/CTX-PL/pC27 against glioma were assessed using the BMVECs/C6 cells co-culture model and the rat orthotopic glioma model. The OX26/CTX-PL/pDNA complexes exhibited a subglobose shape, and possessed notably low toxicities to HEK293T and C6 cells post 4 h incubation. In the in vitro transfection experiment, gene expressions of hTERTC27 from C6 and F98 cells were significantly improved by OX26 and CTX modification. Our in vitro results also showed that OX26 endowed the PLs with the transport ability across the BBB. Using the BMVECs/C6 cells co-culture model, the viability of C6 cells was decreased to 46.0% after OX26/CTX-PL/pC27 transfection. The OX26/CTX-PL/pC27 complexes exhibited enhanced therapeutic effects on C6 cells. Moreover, the dual-targeting therapeutic effects were further conformed with diminished tumor volumes (18.81 ± 6.15 mm3) and extended median survival time (46 days) in C6 glioma-bearing rats. Immunohistochemical analysis revealed the therapeutic effects derived from enhanced hTERTC27 expression in the tumor site. The PEGylated liposomes modified with OX26 and CTX are able to significantly promote cell transfection, increase the transport of plasmid DNA across the BBB and afterwards target the brain glioma cells in vitro and in vivo, exhibit the most significant therapeutic efficacy. The ligand OX26 plays a critical role in transporting the lipoplexes across the BBB, and CTX acts as a major role in targeting brain glioma cells. The results would encourage further developments for non-invasive targeting therapy of brain gliomas by intravenous injection.
Differences in maternal lineages of New Zealand Black mice defined by restriction endonuclease analysis of mitochondrial DNA and by expression of maternally transmitted antigen.
Authors: M M Huston, R Smith, D P Huston, R R Rich
Journal: The Journal of Experimental Medicine (1983)

Two substrains of New Zealand Black (NZB) mice have been compared with respect to expression of a maternally transmitted cell surface antigen, Mta, defined by cloned cytolytic T cells, and for restriction enzyme polymorphisms of mitochondrial DNA (mtDNA). These independent assays of maternal cytoplasmic inheritance provide strong evidence for genetic contamination of the NZB/BlPt substrain (NZB/Bl mice from Michael Potter's separate colony at the National Institutes of Health), in which the typical NZB immunologic abnormalities are at least partially ameliorated. The decisive data are the restriction enzyme maps of mtDNA for NZB/BlPt, which were identical with those of the common "old inbred" strains and quite different from those of NZB/BlN (NZB/Bl mice from the breeding facility at the National Institutes of Health). It is probable that the contamination of the NZB/BlPt substrain is related to phenotypic changes in their autoimmune state. More interestingly, the data are consistent with, although they do not prove, involvement of the mitochondrial genome in expression of a cell surface molecule.
THE TREATMENT OF DIABETIC RETINOPATHY
Authors: E Ai, P Coonan
Journal: Annual Review of Medicine (1987)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
Clonidine in Patients Undergoing Noncardiac Surgery
Authors: P J Devereaux, Daniel I Sessler, Kate Leslie, Andrea Kurz, Marko Mrkobrada, Pablo Alonso-Coello, Juan Carlos Villar, Alben Sigamani, Bruce M Biccard, Christian S Meyhoff, Joel L Parlow, Gordon Guyatt, Andrea Robinson, Amit X Garg, Reitze N Rodseth, Fernando Botto, Giovanna Lurati Buse, Denis Xavier, Matthew T V Chan, Maria Tiboni, Deborah Cook, Priya A Kumar, Patrice Forget, German Malaga, Edith Fleischmann, Mohammed Amir, John Eikelboom, Richard Mizera, David Torres, C Y Wang, Tomas Vanhelder, Pilar Paniagua, Otavio Berwanger, Sadeesh Srinathan, Michelle Graham, Laura Pasin, Yannick Le Manach, Peggy Gao, Janice Pogue, Richard Whitlock, André Lamy, Clive Kearon, Clara Chow, Shirley Pettit, Susan Chrolavicius, Salim Yusuf
Journal: New England Journal of Medicine (2014)

Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability.We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days.Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P<0.001). Clonidine, as compared with placebo, was associated with an increased rate of nonfatal cardiac arrest (0.3% [16 patients] vs. 0.1% [5 patients]; hazard ratio, 3.20; 95% CI, 1.17 to 8.73; P=0.02).Administration of low-dose clonidine in patients undergoing noncardiac surgery did not reduce the rate of the composite outcome of death or nonfatal myocardial infarction; it did, however, increase the risk of clinically important hypotension and nonfatal cardiac arrest. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.).
S99 Multiple regression analyses in a cohort of hereditary haemorrhagic telangiectasia patients suggest a novel role for iron in thrombosis
Authors: J. A. Livesey, J. E. Jackson, C. L. Shovlin
Journal: Thorax (2010)

<h3>Introduction/objectives</h3> Pulmonary emboli (PE) secondary to deep venous thromboses (DVT) are the immediate cause of 10% of hospital deaths. Elevated basal plasma coagulation factor (F) VIII levels, now known to be synthesised by the pulmonary endothelium,1 are the strongest predictor of recurrent PE/DVT, and also associated with elevated pulmonary artery pressure (PAP). The reasons for these associations are unknown. The study objectives were to determine whether novel patient-specific factors were associated with FVIII levels; PE/DVT; and/or PAP. <h3>Methods</h3> Previous studies from our group have presented data on the 1999–2005 hereditary haemorrhagic telangiectasia (HHT) cohort of patients. In the current study, a replicate data series was generated from individuals seen between 2006 and 2010, and analysed independently to the first. Basal plasma FVIII measurements taken at least 4 months from any thrombotic event/intercurrent illness; and 32 patient-specific variables from 221 individuals, including catheter-measured PAP and verified DVT/PE, were entered into an Excel chart. Following verification, data were analysed using STATA v11c (Statacorp LP) software. Univariate analyses identified potentially associated variables, which were analysed using stepwise multiple regression analyses, to generate best-fit models. <h3>Results</h3> For FVIII, the most significant independent variables were identified as fibrinogen, age, and iron replacement therapy (IRT) (model: 4df; p&lt;0.0001; r<sup>2</sup> 0.2014). Fibrinogen showed the most significant association with FVIII (OR 0.193, p&lt;0.001). FVIII showed further associations with age (OR 0.006, p=0.028) and IRT (OR 0.162; p=0.075). PE/DVT was associated with IRT (OR 1.416, p=0.028). Mean PAP was associated with age (OR 0.079, p=0.007) and FVIII (OR 1.449, p=0.009)<i>.</i> Iron deficiency did not emerge as significant in any model. SIREs software predicted specific iron response elements (IREs) in FVIII mRNA splice-variants, including one in the 5′UTR of splice-variant 2.<sup>1</sup> <h3>Conclusions</h3> This study suggests that basal plasma FVIII levels, and associated clinical endpoints of PE/DVT and PAP, may be influenced by iron replacement therapy, possibly by modulating expression of specific splice-variants of the <i>F8</i> gene. This study therefore suggests that iron replacement may increase thrombotic risk, with significant potential clinical implications for millions of people who take iron tablets.
How unitary is the capacity-limited attentional focus?
Authors: Torsten Schubert, Peter A. Frensch
Journal: Behavioral and Brain Sciences (2001)

Cowan assumes a unitary capacity-limited attentional focus. We argue that two main problems need to be solved before this assumption can complement theoretical knowledge about human cognition. First, it needs to be clarified what exactly the nature of the elements (chunks) within the attentional focus is. Second, an elaborated process model needs to be developed and testable assumptions about the proposed capacity limitation need to be formulated.