tbuckley/cabot-search huggingface dataset:
Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of Scottish men with 21 years of follow up
Authors: C. L Hart, G. D. Smith, D. J Hole, V. M Hawthorne
Journal: BMJ (1999)

<h3>Objectives</h3> To assess the impact of physicians' patient base composition on all-cause mortality among people living with HIV (PLHIV) who initiated highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada. <h3>Design</h3> Observational cohort study from 1 January 2000 to 31 December 2013. <h3>Setting</h3> BC Centre for Excellence in HIV/AIDS' (BC-CfE) Drug Treatment Program, where HAART is available at no cost. <h3>Participants</h3> PLHIV aged ≥ 19 who initiated HAART in BC in the HAART Observational Medical Evaluation and Research (HOMER) Study. <h3>Outcome measures</h3> All-cause mortality as determined through monthly linkages to the BC Vital Statistics Agency. <h3>Statistical analysis</h3> We examined the relationships between patient characteristics, physicians' patient base composition, the location of the practice, and physicians' experience with PLHIV and all-cause mortality using unadjusted and adjusted Cox proportional hazards models. <h3>Results</h3> A total of 4 445 PLHIV (median age = 42, Q1, Q3 = 34–49; 80% male) were eligible for our study. Patients were seen by 683 prescribing physicians with a median experience of 77 previously treated PLHIV in the past 2 years (Q1, Q3 = 23–170). A multivariable Cox model indicated that the following factors were associated with all-cause mortality: age (aHR = 1.05 per 1-year increase, 95% CI = 1.04 to 1.06), year of HAART initiation (2004–2007: aHR = 0.65, 95% CI = 0.53 to 0.81, 2008-2011: aHR = 0.46, 95% CI = 0.35 to 0.61, Ref: 2000–2003), CD4 cell count at baseline (aHR = 0.88 per 100-unit increase in cells/mm<sup>3</sup>, 95% CI = 0.82 to 0.94), and &lt; 95% adherence in first year on HAART (aHR = 2.28, 95% CI = 1.88 to 2.76). In addition, physicians' patient base composition, specifically, the proportion of patients who have a history of injection drug use (aHR = 1.11 per 10% increase in the proportion of patients, 95% CI = 1.07 to 1.15) or Indigenous ancestry (aHR = 1.07 per 10% increase , 95% CI = 1.03–1.11) and being a patient of a physician who primarily serves individuals outside of the Vancouver Coastal Health Authority region (aHR = 1.22, 95% CI = 1.01 to 1.47) were associated with mortality. <h3>Conclusions</h3> Our findings suggest that physicians with a higher proportion of individuals who face potential barriers to care may need additional supports to decrease mortality among their patients. Future research is required to examine these relationships in other settings and to determine strategies that may mitigate the associations between the composition of physicians' patient bases and survival.
Respiration and glucose oxidation in human and guinea pig leukocytes: comparative studies
Authors: Robert L. Baehner, Neal Gilman, Manfred L. Karnovsky
Journal: Journal of Clinical Investigation (1970)

A comparison has been made of the metabolic shifts in human and guinea pig leukocytes when they phagocytize. Respiration of guinea pig polymorphonuclear leukocytes (PMN) and the increment during phagocytosis were each about 2(1/2)-fold that of human PMN. This was also true of the direct oxidation of glucose-6-P (hexose monophosphate shunt). Enzymes potentially responsible for these phenomena have been compared in each species. Cyanide-insensitive NADH oxidase and NADPH oxidase were measured and only the formed exhibited adequate activity to account for the respiratory stimulus durintg phagocytosis. The hydrogen peroxide formed by this enzyme stimulates the hexose monophosphate shunt by oxidizing glutathione which upon reduction by an NADPH-linked glutathione reductase provides NADP to drive the hexose monophosphate shunt. Other linkages between respiratory stimulation and that of the hexose monophosphate shunt also pertain in the guinea pig.
ATF3 Suppresses Metastasis of Bladder Cancer by Regulating Gelsolin-Mediated Remodeling of the Actin Cytoskeleton
Authors: Xiangliang Yuan, Liang Yu, Junhua Li, Guohua Xie, Tingting Rong, Liang Zhang, Jianhua Chen, Qiaohong Meng, Aaron T. Irving, Die Wang, Elizabeth D. Williams, Jun-Ping Liu, Anthony J. Sadler, Bryan R.G. Williams, Lisong Shen, Dakang Xu
Journal: Cancer Research (2013)

Bladder cancer is associated with high recurrence and mortality rates due to metastasis. The elucidation of metastasis suppressors may offer therapeutic opportunities if their mechanisms of action can be elucidated and tractably exploited. In this study, we investigated the clinical and functional significance of the transcription factor activating transcription factor 3 (ATF3) in bladder cancer metastasis. Gene expression analysis revealed that decreased ATF3 was associated with bladder cancer progression and reduced survival of patients with bladder cancer. Correspondingly, ATF3 overexpression in highly metastatic bladder cancer cells decreased migration in vitro and experimental metastasis in vivo. Conversely, ATF3 silencing increased the migration of bladder cancer cells with limited metastatic capability in the absence of any effect on proliferation. In keeping with their increased motility, metastatic bladder cancer cells had increased numbers of actin filaments. Moreover, ATF3 expression correlated with expression of the actin filament severing protein gelsolin (GSN). Mechanistic studies revealed that ATF3 upregulated GSN, whereas ATF3 silencing reduced GSN levels, concomitant with alterations in the actin cytoskeleton. We identified six ATF3 regulatory elements in the first intron of the GSN gene confirmed by chromatin immunoprecipitation analysis. Critically, GSN expression reversed the metastatic capacity of bladder cancer cells with diminished levels of ATF3. Taken together, our results indicate that ATF3 suppresses metastasis of bladder cancer cells, at least in part through the upregulation of GSN-mediated actin remodeling. These findings suggest ATF3 coupled with GSN as prognostic markers for bladder cancer metastasis.
Use of Sequential Bayesian Model in Diagnosis of Jaundice by Computer
Authors: R. P. Knill-Jones, R. B. Stern, D. H. Girmes, J. D. Maxwell, R. P. H. Thompson, R. Williams
Journal: BMJ (1973)

A sequential Bayesian model has been developed for a computer and used to diagnose jaundiced patients admitted to hospital. Up to 102 items of information from the history, physical examination, and special investigations available within 48 hours of admission were collected on 309 patients. The results from these patients were used to calculate the probabilities of 11 possible diseases in 65 new patients and also to place patients into groups for medical or surgical treatment. The overall accuracy of the model in diagnosing patients as having one of 11 diseases was 69%, and where the final probability reached &gt; 0·96, it was 89%. The overall accuracy in making a medical or surgical decision was 89%, and where the final probability reached &gt; 0·96 it was 94%. Improvement in accuracy should result as the number of cases seen with rare conditions increases, and probably a similar model could be developed and used to make most use of those indicants with the highest cost-effectiveness.
Vitamin E supplementation and macular degeneration: randomised controlled trial
Authors: H. R Taylor
Journal: BMJ (2002)

<b>Objective</b>: To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD). <b>Design</b>: Prospective randomised placebo controlled clinical trial. <b>Setting</b>: An urban study centre in a residential area supervised by university research staff. <b>Participants</b>: 1193 healthy volunteers aged between 55 and 80 years; 73% completed the trial on full protocol. <b>Interventions</b>: Vitamin E 500 IU or placebo daily for four years. <b>Main outcome measures</b>: Primary outcome: development of early age related macular degeneration in retinal photographs. Other measures included alternative definitions of age related macular degeneration, progression, changes in component features, visual acuity, and visual function <b>Results</b>: The incidence of early age related macular degeneration (early AMD 3) was 8.6% in those receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95% confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus 0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in secondary outcomes. <b>Conclusion</b>: Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration.
New Gianturco-Grifka Vascular Occlusion Device
Authors: Ronald G. Grifka, Charles E. Mullins, Cesare Gianturco, Michael R. Nihill, Martin P. O’Laughlin, Michael C. Slack, Fred J. Clubb, Timothy J. Myers
Journal: Circulation (1995)

Background Transcatheter closure of cardiovascular defects remains a challenge. Several occlusion devices are available, but each device has limitations. The purpose of this study was to evaluate the new Gianturco-Grifka vascular occlusion device (GGVOD) in a canine model. Methods and Results A total of 26 GGVODs were implanted as part of short- and long-term studies. In the short-term study, 1 GGVOD was implanted in each of 11 systemic arteries from 3.2 to 9.0 mm in diameter. All 11 arteries were occluded immediately. In the long-term study, an aortopulmonary shunt was placed in 10 dogs (9, Gore-tex graft; 1, subclavian artery) followed by GGVOD implantation; additionally, a GGVOD was implanted in 5 subclavian arteries. The dogs were boarded for 3 to 6 months, then recatheterized and euthanatized. Immediately after implantation, the 5 subclavian arteries and 9 Gore-tex shunts were occluded completely; the 1 subclavian artery shunt had a small residual leak. At recatheterization, all 10 shunts and 5 subclavian arteries were occluded completely. Necropsy revealed all shunts to be occluded, with the aortic and pulmonic orifices covered with a neointimal layer. The mean fluoroscopic time needed for GGVOD implantation was 9 minutes (range, 3 to 22 minutes). Conclusions (1) In a canine model, the GGVOD is effective for transcatheter occlusion of arteries and aortopulmonary shunts from 3 to 9 mm in diameter. Possible indications in children include aortopulmonary collateral vessels, long patent ductus arteriosus, systemic-pulmonary shunts, AV malformations, and arteries supplying tumors. (2) GGVOD implantation requires a short fluoroscopic time.
Outcome and prognostic factors in patients with mantle-cell lymphoma relapsing after autologous stem-cell transplantation: a retrospective study of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: S. Dietrich, A. Boumendil, H. Finel, I. Avivi, L. Volin, J. Cornelissen, R.J. Jarosinska, C. Schmid, J. Finke, W.B.C. Stevens, H.C. Schouten, M. Kaufmann, C. Sebban, M. Trneny, G. Kobbe, L.M. Fornecker, J. Schetelig, E. Kanfer, T. Heinicke, M. Pfreundschuh, J.L. Diez-Martin, D. Bordessoule, S. Robinson, P. Dreger
Journal: Annals of Oncology (2014)
Telomeric Recombination in Mismatch Repair Deficient Human Colon Cancer Cells after Telomerase Inhibition
Authors: Oliver E. Bechter, Ying Zou, William Walker, Woodring E. Wright, Jerry W. Shay
Journal: Cancer Research (2004)

Abstract The majority of human malignancies use telomerase to maintain telomere homeostasis. Antitelomerase therapy is therefore a promising approach for a cancer-specific therapy. The alternative lengthening of telomeres pathway (ALT) is a recombination-based, telomerase-independent mechanism of telomere length control. It is widely believed that ALT could be engaged when cancer cells escape from telomerase inhibition. However, no reports exist that would support this concept of therapy resistance. We inhibited telomerase in a human cancer cell line with a mismatch repair defect and observed a telomerase-independent, ALT-like telomere elongation. This is the first report of inducing a telomerase-independent telomere elongation in human cancer cells when telomerase is inhibited, thus describing a novel mechanism of resistance to antitelomerase therapy.
Flexible Intensive Insulin Therapy in Adults With Type 1 Diabetes and High Risk for Severe Hypoglycemia and Diabetic Ketoacidosis
Authors: Mary E. Pennant, Mark D. Chatfield, W. Andy Coward, Les J.C. Bluck
Journal: Diabetes Care (2007)

The recent subgroup analysis by Samann et al. (1) examined the effectiveness of diabetes treatment and teaching programs (DTTPs) and advocated intensive insulin therapy combined with increased dietary freedom in individuals with type 1 diabetes who were at increased risk of hypoglycemia. There were significant reductions in hypoglycemic episodes, from 6.1 to 1.4 hypoglycemic events per patient per year, after participation. Samann et al. concluded that DTTPs may reduce the occurrence of hypoglycemic episodes for those at risk, but, for several reasons, this …
Breast Cancer Metastasis Suppressor 1 Up-regulates miR-146, Which Suppresses Breast Cancer Metastasis
Authors: Douglas R. Hurst, Mick D. Edmonds, Gary K. Scott, Christopher C. Benz, Kedar S. Vaidya, Danny R. Welch
Journal: Cancer Research (2009)

Abstract Breast cancer metastasis suppressor 1 (BRMS1) is a predominantly nuclear protein that differentially regulates expression of multiple genes, leading to suppression of metastasis without blocking orthotopic tumor growth in multiple human and murine cancer cells of diverse origins. We hypothesized that miR-146 may be involved in the ability of BRMS1 to supress metastasis because miR-146 expression is altered by BRMS1 and because BRMS1 and miR-146 are both associated with decreased signaling through the nuclear factor-κB pathway. BRMS1 significantly up-regulates miR-146a by 6- to 60-fold in metastatic MDA-MB-231 and MDA-MB-435 cells, respectively, and miR-146b by 40-fold in MDA-MB-435 as measured by real-time quantitative reverse transcription-PCR. Transduction of miR-146a or miR-146b into MDA-MB-231 down-regulated expression of epidermal growth factor receptor, inhibited invasion and migration in vitro, and suppressed experimental lung metastasis by 69% and 84%, respectively (mean ± SE: empty vector = 39 ± 6, miR-146a = 12 ± 1, miR-146b = 6 ± 1). These results further support the recent notion that modulating the levels of miR-146a or miR-146b could have a therapeutic potential to suppress breast cancer metastasis. [Cancer Res 2009;69(4):1279–83]
Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units
Authors: J. C Wyatt, S. Paterson-Brown, R. Johanson, D. G Altman, M. J Bradburn, N. M Fisk
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective</b> To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews. <b>Design</b> Randomised single blind controlled trial with obstetric units allocated to an educational visit or control group. <b>Setting</b> 25 of the 26 district general obstetric units in two former NHS regions. <b>Subjects</b> The senior obstetrician and midwife from each intervention unit participated in educational visits. Clinical practices of all staff were assessed in 4508 pregnancies. <b>Intervention</b> Single informal educational visit by a respected obstetrician including discussion of evidence based obstetrics, guidance on implementation, and donation of Cochrane database and other materials. <b>Main outcome measures</b> Rates of perineal suturing with polyglycolic acid, ventouse delivery, prophylactic antibiotics in caesarean section, and steroids in preterm delivery, before and 9 months after visits, and concordance of guidelines with review evidence for same marker practices before and after visits. <b>Results</b> Rates varied greatly, but the overall baseline mean of 43% (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse delivery increased significantly in intervention units but not in control units; there was no difference between the two types of units in uptake of other practices. Pooling rates from all 25 units, use of antibiotics in caesarean section and use of polyglycolic acid sutures increased significantly over the period, but use of steroids in preterm delivery was unchanged. Labour ward guidelines seldom agreed with evidence at baseline; this hardly improved after visits. Educational visits cost 860$ each (at 1995 prices). <b>Conclusions</b> There was considerable uptake of evidence into practice in both control and intervention units between 1994 and 1995. Our educational visits added little to this, despite the informal setting, targeting of senior staff from two disciplines, and donation of educational materials. Further work is needed to define cost effective methods to enhance the uptake of evidence from systematic reviews and to clarify leadership and roles of senior obstetric staff in implementing the evidence.
Neuroanatomy of Down’s Syndrome: A High-Resolution MRI Study
Authors: Joseph D. Pinter, Stephan Eliez, J. Eric Schmitt, George T. Capone, Allan L. Reiss
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: Down’s syndrome, the most common genetic cause of mental retardation, results in characteristic physical and neuropsychological findings, including mental retardation and deficits in language and memory. This study was undertaken to confirm previously reported abnormalities of regional brain volumes in Down’s syndrome by using high-resolution magnetic resonance imaging (MRI), determine whether these volumetric abnormalities are present from childhood, and consider the relationship between neuroanatomic abnormalities and the cognitive profile of Down’s syndrome. METHOD: Sixteen children and young adults with Down’s syndrome (age range=5–23 years) were matched for age and gender with 15 normal comparison subjects. High-resolution MRI scans were quantitatively analyzed for measures of overall and regional brain volumes and by tissue composition. RESULTS: Consistent with prior imaging studies, subjects with Down’s syndrome had smaller overall brain volumes, with disproportionately smaller cerebellar volumes and relatively larger subcortical gray matter volumes. Also noted was relative preservation of parietal lobe gray and temporal lobe white matter in subjects with Down’s syndrome versus comparison subjects. No abnormalities in pattern of brain asymmetry were noted in Down’s syndrome subjects. CONCLUSIONS: The results largely confirm findings of previous studies with respect to overall patterns of brain volumes in Down’s syndrome and also provide new evidence for abnormal volumes of specific regional tissue components. The presence of these abnormalities from an early age suggests that fetal or early postnatal developmental differences may underlie the observed pattern of neuroanatomic abnormalities and contribute to the specific cognitive and developmental deficits seen in individuals with Down’s syndrome.
Mapping of a Gene for Severe Pediatric Gastroesophageal Reflux to Chromosome 13q14
Authors: Fen Ze Hu
Journal: JAMA (2000)

ContextGastroesophageal reflux (GER) has not previously been widely regarded as a hereditary disease. A few reports have suggested, however, that a genetic component may contribute to the incidence of GER, especially in its severe or chronic forms.ObjectiveTo identify a genetic locus that cosegregates with a severe pediatric GER phenotype in families with multiple affected members.DesignA genome-wide scan of families affected by severe pediatric GER using polymorphic microsatellite markers spaced at an average of 8 centimorgans (cM), followed by haplotyping and by pairwise and multipoint linkage analyses.SettingGeneral US community, with research performed in a university tertiary care hospital.SubjectsAffected and unaffected family members from 5 families having multiple individuals affected by severe pediatric GER, identified through a patient support group.Main Outcome MeasuresDetermination of inheritance patterns and linkage of a genetic locus with the severe pediatric GER phenotype by logarithm-of-odds (lod) score analysis, considering a lod score of 3 or greater as evidence of linkage.ResultsIn these families, severe pediatric GER followed an autosomal dominant hereditary pattern with high penetrance. A gene for severe pediatric GER was mapped to a 13-cM region on chromosome 13q between microsatellite markers D13S171 and D13S263. A maximum multifamily 2-point lod score of 5.58 and a maximum multifamily multipoint lod score of 7.15 were obtained for marker D13S1253 at map position 35 cM when presumptively affected persons were modeled as unknown (a maximum multipoint score of 4.88 was obtained when presumptively affected persons were modeled as unaffected).ConclusionThese data suggest that a gene for severe pediatric GER maps to chromosome 13q14.
Novel Role for the Potent Endogenous Inotrope Apelin in Human Cardiac Dysfunction
Authors: Mary M. Chen, Euan A. Ashley, David X.F. Deng, Anya Tsalenko, Alicia Deng, Raymond Tabibiazar, Amir Ben-Dor, Brett Fenster, Eugene Yang, Jennifer Y. King, Michael Fowler, Robert Robbins, Frances L. Johnson, Laurakay Bruhn, Theresa McDonagh, Henry Dargie, Zohar Yakhini, Philip S. Tsao, Thomas Quertermous
Journal: Circulation (2003)

Background— Apelin is among the most potent stimulators of cardiac contractility known. However, no physiological or pathological role for apelin–angiotensin receptor-like 1 (APJ) signaling has ever been described. Methods and Results— We performed transcriptional profiling using a spotted cDNA microarray with 12 814 unique clones on paired samples of left ventricle obtained before and after placement of a left ventricular assist device in 11 patients. The significance analysis of microarrays and a novel rank consistency score designed to exploit the paired structure of the data confirmed that natriuretic peptides were among the most significantly downregulated genes after offloading. The most significantly upregulated gene was the G-protein–coupled receptor APJ, the specific receptor for apelin. We demonstrate here using immunoassay and immunohistochemical techniques that apelin is localized primarily in the endothelium of the coronary arteries and is found at a higher concentration in cardiac tissue after mechanical offloading. These findings imply an important paracrine signaling pathway in the heart. We additionally extend the clinical significance of this work by reporting for the first time circulating human apelin levels and demonstrating increases in the plasma level of apelin in patients with left ventricular dysfunction. Conclusions— The apelin-APJ signaling pathway emerges as an important novel mediator of cardiovascular control.
687 CLAUDIN-1, A TIGHT JUNCTION PROTEIN INVOLVED IN NISCH SYNDROME, PLAYS A ROLE IN HEPATIC PARACELLULAR PERMEABILITY: EVIDENCE IN HEPATOCELLULAR AND CHOLANGIOCELLULAR POLARIZED LINES
Authors: P. Cassio, B. Grosse, N. Yousef, E. Gonzales, E. Jacquemin
Journal: Journal of Hepatology (2011)