tbuckley/cabot-search huggingface dataset:
Psychological Impact of Screening for Familial Ovarian Cancer
Authors: F. J. Wardle, W. Collins, A. L. Pernet, M. I. Whitehead, T. H. Bourne, S. Campbell
Journal: JNCI Journal of the National Cancer Institute (1993)

Psychological distress following false-positive results could constitute a substantial disadvantage of cancer screening.The purpose of this prospective study was to evaluate the psychological impact of true-negative and false-positive results in a high-risk group of women in a screening program to detect early familial ovarian cancer by ovarian ultrasound scan. The influence of coping style was also assessed.Of 500 women who contacted the nationally advertised screening program, 302 received the scan and participated in the study. Before the screening, they were mailed a questionnaire concerning psychological state, coping style, and anxiety about risk of cancer. Transabdominal ultrasonography and transvaginal ultrasonography with color Doppler imaging were used to detect persistent ovarian lesions and changes in volume. Women were informed of any abnormality immediately and asked to return for another scan after 6 weeks. Those with a persistent ovarian mass were referred for hysterectomy and bilateral oophorectomy. The questionnaire was used to reassess psychological distress after the first ultrasound scan, after re-scanning, and after surgery.The first scan showed negative results for 233 of the 302 women; 69 (23%) had abnormalities in ovarian morphology. Sixty-four of the 69 had a second scan, with negative results for 32 and equivocal results for 12; 20 had surgery because the results of both scans were positive. None of the patients in the screening program were found to have ovarian cancer. After the first scan, psychological distress and worries about cancer were significantly reduced (P < .001) in the women who had negative results. Responses to positive results depended on the baseline coping style and the clinician's appraisal of malignancy potential at the time of the scan. Women who had information-seeking coping styles and those who were referred for surgery had higher levels of distress than other women. At follow-up, the anxiety scores of women who had positive results on both scans but negative results at surgery had returned to baseline levels.The findings suggest that false-positive results in screening are associated with increased distress in the short term, but these adverse effects do not appear to be severe or persistent. Women who had surgery appeared to welcome the certainty that they could never develop ovarian cancer.The issue of continued surveillance needs to be addressed, since many women expressed the desire to have the scan repeated regularly.
Human autoantibodies to poly(adenosine diphosphate-ribose) polymerase.
Authors: H Yamanaka, E H Willis, C A Penning, C L Peebles, E M Tan, D A Carson
Journal: Journal of Clinical Investigation (1987)

The chromatin-bound enzyme poly(ADP-ribose) polymerase (ADPRP) is strongly stimulated by DNA with single- or double-stranded breaks, and transfers the ADP-ribose moiety of NAD to nuclear proteins. The activation of ADPRP is important for DNA repair and replication, and also has been postulated to play a role in the pathogenesis of lymphocyte dysfunction associated with chronic inflammatory diseases, and inborn errors of nucleoside metabolism. We have detected high titers of IgG autoantibodies to the ADPRP protein in six patients with rheumatic complaints. No other autoantibodies were detected in any of the six sera. The specificity of the anti-enzyme antibodies was established by (a) immunoprecipitation of ADPRP activity, (b) immunoprecipitation and immunoblotting of both the native 116-kD enzyme and its proteolytic digestion products. ADPRP was purified from human thymus and calf thymus. The autoantibodies reacted equivalently with both enzymes. The anti-ADPRP antibodies had a distinctive immunofluorescent pattern with HEp-2 cells, reacting intensely with nucleoli and metaphase chromosomes, and diffusely with the nucleus. Autoantibodies to ADPRP have not been described previously. The presence of a specific immune response against an enzyme that has been associated with various immunodeficiency syndromes raises intriguing possibilities concerning the relationship between DNA damage, immunodeficiency, and autoimmunity.
Identification of motifs that function in the splicing of non-canonical introns
Authors: Jill I Murray, Rodger B Voelker, Kristy L Henscheid, M. BRYAN Warf, J. ANDREW Berglund
Journal: Genome biology (2008)

While the current model of pre-mRNA splicing is based on the recognition of four canonical intronic motifs (5' splice site, branchpoint sequence, polypyrimidine (PY) tract and 3' splice site), it is becoming increasingly clear that splicing is regulated by both canonical and non-canonical splicing signals located in the RNA sequence of introns and exons that act to recruit the spliceosome and associated splicing factors. The diversity of human intronic sequences suggests the existence of novel recognition pathways for non-canonical introns. This study addresses the recognition and splicing of human introns that lack a canonical PY tract. The PY tract is a uridine-rich region at the 3' end of introns that acts as a binding site for U2AF65, a key factor in splicing machinery recruitment. Human introns were classified computationally into low- and high-scoring PY tracts by scoring the likely U2AF65 binding site strength. Biochemical studies confirmed that low-scoring PY tracts are weak U2AF65 binding sites while high-scoring PY tracts are strong U2AF65 binding sites. A large population of human introns contains weak PY tracts. Computational analysis revealed many families of motifs, including C-rich and G-rich motifs, that are enriched upstream of weak PY tracts. In vivo splicing studies show that C-rich and G-rich motifs function as intronic splicing enhancers in a combinatorial manner to compensate for weak PY tracts. The enrichment of specific intronic splicing enhancers upstream of weak PY tracts suggests that a novel mechanism for intron recognition exists, which compensates for a weakened canonical pre-mRNA splicing motif.
Glucocorticoid resistant asthma: T-lymphocyte steroid metabolism and sensitivity to glucocorticoids and immunosuppressive agents
Authors: CJ Corrigan, JK Bungre, B Assoufi, AE Cooper, H Seddon, AB Kay
Journal: European Respiratory Journal (1996)

We have previously shown that T-lymphocytes from clinically glucocorticoid (GC) resistant asthmatics are more refractory to dexamethasone suppression in vitro than those of GC sensitive asthmatics. We wished to extend these observations to compare three GCs used topically for asthma therapy (budesonide, beclomethasone dipropionate and fluticasone 17 alpha-propionate) and three immunosuppressive drugs (cyclosporin A, FK506 (tacrolimus) and mycophenolate mofetil) with dexamethasone for their antiproliferative effects on T-lymphocytes from GC sensitive and resistant asthmatics, and also to compare the rates of steroid metabolism by T-lymphocytes from these patients. Antiproliferative activity of the drugs was measured on peripheral blood T-lymphocytes activated with phytohaemagglutinin (PHA) and anti-CD3 antibody in vitro. The rates of total steroid metabolism and 20 alpha-hydroxylation by T-cell homogenates were measured using radiolabelled progesterone as an established probe substrate. Over a wide concentration range, T-lymphocytes from GC resistant asthmatics were significantly less inhibited by all four GCs as compared with cells from GC sensitive asthmatics. The median inhibitory concentrations (IC50) for inhibition of T-lymphocytes from the GC resistant asthmatics exceeded those likely to be achieved therapeutically by systemic administration (although higher concentrations might in theory be achieved locally in the bronchial mucosa by inhaled administration). In contrast, all three immunosuppressive drugs at putative therapeutic concentrations inhibited T-lymphocytes both from GC sensitive and resistant asthmatics with equivalent potency. The rates of total metabolism and 20 alpha-hydroxylation of steroid by homogenates of T-lymphocytes from GC sensitive and resistant asthmatics were equivalent. Thus, relative GC resistance in T-lymphocytes from GC resistant as compared with sensitive asthmatics is: 1) manifest with GC molecules of variable molecular structure; 2) not accompanied by elevated intracellular metabolism of steroids; and 3) overcome by immunosuppressive drugs which inhibit T-lymphocytes by non-GC-mediated mechanisms. We conclude that current anti-asthma glucocorticoids at therapeutic concentrations are unlikely to be of benefit for the therapy of glucocorticoid resistant asthma, and that other immunosuppressive drugs may have potential as therapeutic agents in these patients.
10 year follow up study of mortality among users of hostels for homeless people in Copenhagen
Authors: M. Nordentoft
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives</b> To investigate mortality among users of hostels for homeless people in Copenhagen, and to identify predictors of death such as conditions during upbringing, mental illness, and misuse of alcohol and drugs. <b>Design</b> Register based follow up study. <b>Setting</b> Two hostels for homeless people in Copenhagen, Denmark <b>Participants</b> 579 people who stayed in one hostel in Copenhagen in 1991, and a representative sample of 185 people who stayed in the original hostel and one other in Copenhagen. <b>Main outcome measure</b> Cause specific mortality. <b>Results</b> The age and sex standardised mortality ratio for both sexes was 3.8 (95% confidence interval 3.5 to 4.1); 2.8 (2.6 to 3.1) for men and 5.6 (4.3 to 6.9) for women. The age and sex standardised mortality ratio for suicide for both sexes was 6.0 (3.9 to 8.1), for death from natural causes 2.6 (2.3 to 2.9), for unintentional injuries 14.6 (11.4 to 17.8), and for unknown cause of death 62.9 (52.7 to 73.2). Mortality was comparatively higher in the younger age groups. It was also significantly higher among homeless people who had stayed in a hostel more than once and stayed fewer than 11 days, compared with the rest of the study group. Risk factors for early death were premature death of the father and misuse of alcohol and sedatives. <b>Conclusion</b> Homeless people staying in hostels, particularly young women, are more likely to die early than the general population. Other predictors of early death include adverse experiences in childhood, such as death of the father, and misuse of alcohol and sedatives.
DAMAGE TO POLYMER SURFACE AND DETACHMENT OF POLYMER FRAGMENTS DURING DELIVERY BALLOON EXPANSION OF DRUG-ELUTING STENTS: A PREVIOUSLY UNRECOGNIZED SOURCE FOR ADVERSE OUTCOMES
Authors: Scott J. Denardo, Paul L. Carpinone, David M. Vock, James E. Tcheng, Harry R. Phillips, III, Christopher D. Batich, Carl J. Pepine
Journal: Journal of the American College of Cardiology (2012)
Cardiac Dysfunction and Mortality in HIV-Infected Children
Authors: Steven E. Lipshultz, Kirk A. Easley, E. John Orav, Samuel Kaplan, Thomas J. Starc, J. Timothy Bricker, Wyman W. Lai, Douglas S. Moodie, George Sopko, Steven D. Colan
Journal: Circulation (2000)

Background —Left ventricular (LV) dysfunction is common in children infected with the human immunodeficiency virus (HIV), but its clinical importance is unclear. Our objective was to determine whether abnormalities of LV structure and function independently predict all-cause mortality in HIV-infected children. Methods and Results —Baseline echocardiograms were obtained on 193 children with vertically transmitted HIV infection (median age, 2.1 years). Children were followed up for a median of 5 years. Cox regression was used to identify measures of LV structure and function predictive of mortality after adjustment for other important demographic and baseline clinical risk factors. The time course of cardiac variables before mortality was also examined. The 5-year cumulative survival was 64%. Mortality was higher in children who, at baseline, had depressed LV fractional shortening (FS) or contractility; increased LV dimension, thickness, mass, or wall stress; or increased heart rate or blood pressure ( P ≤0.02 for each). Decreased LV FS ( P &lt;0.001) and increased wall thickness ( P =0.004) were also predictive of increased mortality after adjustment for CD4 count ( P &lt;0.001), clinical center ( P &lt;0.001), and encephalopathy ( P &lt;0.001). FS showed abnormalities for up to 3 years before death, whereas wall thickness identified a population at risk only 18 to 24 months before death. Conclusions —Depressed LV FS and increased wall thickness are risk factors for mortality in HIV-infected children independent of depressed CD4 cell count and neurological disease. FS may be useful as a long-term predictor and wall thickness as a short-term predictor of mortality.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 11
Authors: J R Poortmans, E S Rawson, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2010)

Those who are old enough to have been working in the world of sports science/medicine in 1992 will remember a watershed moment: the publication of a paper by Roger Harris and co-workers1 on the capacity of the muscle to increase its phosphocreatine concentration following supplementation with a creatine product. With the genie out of the bottle, we bore witness to an explosion of interest in this unique ergogenic aid—a product of apparently genuine value to biochemists, sports scientists, athletes, coaches, clinicians and the supplement industry. This review will outline why the production and sales of creatine have increased exponentially over the past two decades, and will summarise which of the claims made about creatine supplements are evidence based.

### J R Poortmans, E S Rawson

Creatine, a derivative from three amino acids, is distributed at approximately 95% in skeletal muscle mass; the remainder is located in the brain, the testes and the kidneys. Its synthesis starts mainly in the kidneys from glycine and arginine, forming α-methylguanidoacetic acid, which is conducted through the blood to the liver where it reacts with S-adenosylmethionine to synthesise creatine. Approximately 1–2 g of creatine is produced over 24 h and released mainly to the skeletal muscle system. Some creatine is also added to the pool by adequate dietary intake, predominantly from meat and fish, with a typical diet supplying approximately 1–2 g of …
Suppression of innate immunity (natural killer cell/interferon-γ) in the advanced stages of liver fibrosis in mice
Authors: Won-Il Jeong, Ogyi Park, Yang-Gun Suh, Jin-Seok Byun, So-Young Park, Earl Choi, Ja-Kyung Kim, Hyojin Ko, Hua Wang, Andrew M. Miller, Bin Gao
Journal: Hepatology (2011)

Activation of innate immunity (natural killer [NK] cell/interferon-γ [IFN-γ]) has been shown to play an important role in antiviral and antitumor defenses as well as antifibrogenesis. However, little is known about the regulation of innate immunity during chronic liver injury. Here, we compared the functions of NK cells in early and advanced liver fibrosis induced by a 2-week or a 10-week carbon tetrachloride (CCl4) challenge, respectively. Injection of polyinosinic-polycytidylic acid (poly I:C) or IFN-γ induced NK cell activation and NK cell killing of hepatic stellate cells (HSCs) in the 2-week CCl4 model. Such activation was diminished in the 10-week CCl4 model. Consistent with these findings, the inhibitory effect of poly I:C and IFN-γ on liver fibrosis was markedly reduced in the 10-week versus the 2-week CCl4 model. In vitro coculture experiments demonstrated that 4-day cultured (early activated) HSCs induce NK cell activation via an NK group 2 member D/retinoic acid-induced early gene 1-dependent mechanism. Such activation was reduced when cocultured with 8-day cultured (intermediately activated) HSCs due to the production of transforming growth factor-β (TGF-β) by HSCs. Moreover, early activated HSCs were sensitive, whereas intermediately activated HSCs were resistant to IFN-γ-mediated inhibition of cell proliferation, likely due to elevated expression of suppressor of cytokine signaling 1 (SOCS1). Disruption of the SOCS1 gene restored the IFN-γ inhibition of cell proliferation in intermediately activated HSCs. Production of retinol metabolites by HSCs contributed to SOCS1 induction and subsequently inhibited IFN-γ signaling and functioning, whereas production of TGF-β by HSCs inhibited NK cell function and cytotoxicity against HSCs. Conclusion: The antifibrogenic effects of NK cell/IFN-γ are suppressed during advanced liver injury, which is likely due to increased production of TGF-β and expression of SOCS1 in intermediately activated HSCs. (HEPATOLOGY 2011;)
Lipid and Lipoprotein Profiles in Youth With and Without Type 1 Diabetes
Authors: John Guy, Lorraine Ogden, R. Paul Wadwa, Richard F. Hamman, Elizabeth J. Mayer-Davis, Angela D. Liese, Ralph D'Agostino, Santica Marcovina, Dana Dabelea
Journal: Diabetes Care (2008)

The purpose of this study was to compare the lipid profile and the prevalence of lipid abnormalities in youth with and without type 1 diabetes and explore the role of glycemic control on the hypothesized altered lipid profile in youth with type 1 diabetes.We conducted a cross-sectional analysis of 512 youth with type 1 diabetes (mean duration 4.22 years) and 188 healthy control subjects aged 10-22 years in Colorado and South Carolina. SEARCH for Diabetes in Youth (SEARCH) participants with type 1 diabetes and healthy control subjects recruited from primary care offices in the same geographic regions were invited to attend a research visit. Fasting lipid profiles were compared between youth with type 1 diabetes (stratified according to categories of optimal [A1C <7.5%] and suboptimal [A1C >or=7.5%] glycemic control) and healthy nondiabetic youth, using multiple linear and logistic regression.Youth with type 1 diabetes and optimal A1C had lipid concentrations that were similar (total cholesterol, LDL cholesterol, and LDL particle size) or even less atherogenic (HDL cholesterol, non-HDL cholesterol, triglyceride, and triglyceride-to-HDL cholesterol ratio) than those observed in nondiabetic youth, whereas youth with suboptimal glycemic control had elevated standard lipid levels (total cholesterol, LDL cholesterol, and non-HDL cholesterol). Youth with type 1 diabetes also had significantly elevated apolipoprotein B levels and more small, dense LDL particles than nondiabetic youth, regardless of glycemic control.Youth with type 1 diabetes have abnormal lipid levels and atherogenic changes in lipoprotein composition, even after a relatively short disease duration. As in adults, glycemic control is an important mediator of these abnormalities.
Propensity-Matched Mortality Comparison of Incident Hemodialysis and Peritoneal Dialysis Patients
Authors: Eric D. Weinhandl, Robert N. Foley, David T. Gilbertson, Thomas J. Arneson, Jon J. Snyder, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2010)

Contemporary comparisons of mortality in matched hemodialysis and peritoneal dialysis patients are lacking. We aimed to compare survival of incident hemodialysis and peritoneal dialysis patients by intention-to-treat analysis in a matched-pair cohort and in subsets defined by age, cardiovascular disease, and diabetes. We matched 6337 patient pairs from a retrospective cohort of 98,875 adults who initiated dialysis in 2003 in the United States. In the primary intention-to-treat analysis of survival from day 0, cumulative survival was higher for peritoneal dialysis patients than for hemodialysis patients (hazard ratio 0.92; 95% CI 0.86 to 1.00, P = 0.04). Cumulative survival probabilities for peritoneal dialysis versus hemodialysis were 85.8% versus 80.7% (P < 0.01), 71.1% versus 68.0% (P < 0.01), 58.1% versus 56.7% (P = 0.25), and 48.4% versus 47.3% (P = 0.50) at 12, 24, 36, and 48 months, respectively. Peritoneal dialysis was associated with improved survival compared with hemodialysis among subgroups with age <65 years, no cardiovascular disease, and no diabetes. In a sensitivity analysis of survival from 90 days after initiation, we did not detect a difference in survival between modalities overall (hazard ratio 1.05; 95% CI 0.96 to 1.16), but hemodialysis was associated with improved survival among subgroups with cardiovascular disease and diabetes. In conclusion, despite hazard ratio heterogeneity across patient subgroups and nonconstant hazard ratios during the follow-up period, the overall intention-to-treat mortality risk after dialysis initiation was 8% lower for peritoneal dialysis than for matched hemodialysis patients. These data suggest that increased use of peritoneal dialysis may benefit incident ESRD patients.
The human macrophage mannose receptor directs <i>Mycobacterium tuberculosis</i> lipoarabinomannan-mediated phagosome biogenesis
Authors: Peter B. Kang, Abul K. Azad, Jordi B. Torrelles, Thomas M. Kaufman, Alison Beharka, Eric Tibesar, Lucy E. DesJardin, Larry S. Schlesinger
Journal: The Journal of Experimental Medicine (2005)

Mycobacterium tuberculosis (M.tb) survives in macrophages in part by limiting phagosome–lysosome (P-L) fusion. M.tb mannose-capped lipoarabinomannan (ManLAM) blocks phagosome maturation. The pattern recognition mannose receptor (MR) binds to the ManLAM mannose caps and mediates phagocytosis of bacilli by human macrophages. Using quantitative electron and confocal microscopy, we report that engagement of the MR by ManLAM during the phagocytic process is a key step in limiting P-L fusion. P-L fusion of ManLAM microspheres was significantly reduced in human macrophages and an MR-expressing cell line but not in monocytes that lack the receptor. Moreover, reversal of P-L fusion inhibition occurred with MR blockade. Inhibition of P-L fusion did not occur with entry via Fcγ receptors or dendritic cell–specific intracellular adhesion molecule 3 grabbing nonintegrin, or with phosphatidylinositol-capped lipoarabinomannan. The ManLAM mannose cap structures were necessary in limiting P-L fusion, and the intact molecule was required to maintain this phenotype. Finally, MR blockade during phagocytosis of virulent M.tb led to a reversal of P-L fusion inhibition in human macrophages (84.0 ± 5.1% vs. 38.6 ± 0.6%). Thus, engagement of the MR by ManLAM during the phagocytic process directs M.tb to its initial phagosomal niche, thereby enhancing survival in human macrophages.
Pulse methylprednisolone therapy for arthritis causing muscle weakness
Authors: E M. Shanahan, M. D Smith, M. J Ahern
Journal: Annals of the Rheumatic Diseases (1999)

The occurrence of multiple autoimmmune conditions in the same patient is a well recognised phenomenon.In this case, we present a patient with an inflammatory arthritis (late onset rheumatoid arthritis) with previously unrecognised myasthenia gravis that was unmasked by high dose intravenous pulse methylprednisolone succinate used to treat the arthritis.