tbuckley/cabot-search huggingface dataset:
Significantly Different Patterns of Amino Acid Replacement After Gene Duplication as Compared to After Speciation
Authors: C. Seoighe
Journal: Molecular Biology and Evolution (2003)

We have performed a large-scale analysis of amino acid sequence evolution after gene duplication by comparing evolution after gene duplication with evolution after speciation in over 1,800 phylogenetic trees constructed from manually curated alignments of protein domains downloaded from the PFAM database. The site-specific rate of evolution is significantly altered by gene duplication. A significant increase in the proportion of amino acid substitutions at constrained (slowly evolving) sites after duplication was observed. An increase in the proportion of replacements at normally constrained amino acid sites could result from relaxation of purifying selective pressure. However, the proportion of amino acid replacements involving radical changes in amino acid properties after duplication does not appear to be significantly increased by relaxed selective pressure. The increased proportion of replacements at constrained sites was observed over a relatively large range of protein change (up to 25% amino acid replacements per site). These findings have implications for our understanding of the nature of evolution after duplication and may help to shed light on the evolution of novel protein functions through gene duplication.
Real-Time Quantification and Display of Skin Radiation During Coronary Angiography and Intervention
Authors: Ad den Boer, Pim J. de Feijter, Patrick W. Serruys, Jos R.T.C. Roelandt
Journal: Circulation (2001)

Radiographically guided investigations may be associated with excessive radiation exposure, which may cause skin injuries. The purpose of this study was to develop and test a system that measures in real time the dose applied to each 1-cm(2) area of skin, taking into account the movement of the x-ray source and changes in the beam characteristics. The goal of such a system is to help prevent high doses that might cause skin injury.The entrance point, beam size, and dose at the skin of the patient were calculated by use of the geometrical settings of gantry, investigation table, and x-ray beam and an ionization chamber. The data are displayed graphically. Three hundred twenty-two sequential cardiac investigations in adult patients were analyzed. The mean peak entrance dose per investigation was 0.475 Gy to a mean skin area of 8.2 cm(2). The cumulative KERMA-area product per investigation was 52.2 Gy/cm(2) (25.4 to 99.2 Gy/cm(2)), and the mean entrance beam size at the skin was 49.2 cm(2). Twenty-eight percent of the patients (90/322) received a maximum dose of <1 Gy to a small skin area ( approximately 6 cm(2)), and 13.5% of the patients (42/322) received a maximum dose of >2 Gy.Monitoring of the dose distribution at the skin will alert the operator to the development of high-dose areas; by use of other gantry settings with nonoverlapping entrance fields, different generator settings, and extra collimation, skin lesion can be avoided.
Transplantation rates for living- but not deceased-donor kidneys vary with socioeconomic status in Australia
Authors: Blair S. Grace, Philip A. Clayton, Alan Cass, Stephen P. McDonald
Journal: Kidney International (2012)

Socioeconomic disadvantage has been linked to reduced access to kidney transplantation. To understand and address potential barriers to transplantation, we used the Australia and New Zealand Dialysis and Transplant Registry and examined primary kidney-only transplantation among adult non-Indigenous patients who commenced chronic renal replacement therapy in Australia during 2000-2010. Socioeconomic status was derived from residential postcodes using standard indices. Among the 21,190 patients who commenced renal replacement therapy, 4105 received a kidney transplant (2058 from living donors (660 preemptive) or 2047 from deceased donors) by the end of 2010. Compared with the most socioeconomic disadvantaged quartile, patients from the most advantaged quartile were more likely to receive a preemptive transplant (relative rate 1.93), and more likely to receive a living-donor kidney (adjusted subhazard ratio 1.34) after commencing dialysis. Socioeconomic status was not associated with deceased-donor transplantation. Thus, the association between socioeconomic status and living- but not deceased-donor transplantation suggests that potential donors (rather than recipients) from disadvantaged areas may face barriers to donation. Although the deceased-donor organ allocation process appears essentially equitable, it differs between Australian states.
Propafenone Preferentially Blocks the Rapidly Activating Component of Delayed Rectifier K <sup>+</sup> Current in Guinea Pig Ventricular Myocytes
Authors: Eva Delpón, Carmen Valenzuela, Onésima Pérez, Oscar Casis, Juan Tamargo
Journal: Circulation Research (1995)

Abstract The effects of propafenone on the delayed rectifier K + current were studied in guinea pig ventricular myocytes by using the patch-clamp technique. In these myocytes, this current consists of at least two components: a La 3+ -sensitive component activating rapidly with moderate depolarizations and a La 3+ -resistant current slowly activating at more positive potentials. In the absence of La 3+ (when both components are present), propafenone inhibited the delayed outward current, its effects being more marked after weak than after strong depolarizations. Propafenone-induced block of the tail currents elicited on return to −30 mV was more marked after short than after long depolarizing pulses. In the presence of 1 μmol/L propafenone, the envelope-of-tails test was satisfied, thus indicating that at this concentration propafenone completely blocks the rapidly activating component. In the presence of La 3+ (when only the slow component is present), the steady state inhibition induced by 5 μmol/L propafenone on both the maximum activated and the tail currents was independent of the test pulse voltage. Development of propafenone-induced block on the slowly activating component was very fast and linked to channel opening. In addition, the blockade appeared to be use dependent, with the rate constant of the onset kinetics at 2 Hz being 0.44±0.1 pulse −1 . The recovery process from propafenone-induced block exhibited a time constant of 2.5±0.4 s. These results indicated that propafenone preferentially inhibits the rapidly activating component of the delayed rectifier and that it blocks in a voltage-independent and time-dependent manner the slow component of this current.
Urinary prostaglandins. Identification and origin.
Authors: J C Frölich, T W Wilson, B J Sweetman, M Smigel, A S Nies, K Carr, J T Watson, J A Oates
Journal: Journal of Clinical Investigation (1975)

Human urine was analyzed by mass spectrometry for the presence of prostaglandins. Prostaglandin E2 and F2alpha were detected in urine from females by selected ion monitoring of the prostaglandin E2-methylester-methoxime bis-acetate and the prostaglandin F2alpha-methyl ester-Tris-trimethylsilylether derivative. Additional evidence for the presence of prostaglandin F2alpha was obtained by isolating from female urine an amount of this prostaglandin sufficient to yield a complete mass spectrum. The methods utilized permitted quantitative analysis. The origin of urinary prostaglandin was determined by stimulating renal prostaglandin synthesis by arachidonic acid or angiotensin infusion. Arachidonic acid, the precursor of prostaglandin E2, when infused into one renal artery of a dog led to a significant increase in the excretion rate of this prostaglandin. Similarly, infusion of angiotensin II amide led to a significantly increased ipsilateral excretion rate of prostaglandin E2 and F2a in spite of a simultaneous decrease in the creatinine clearance. In man, i.v. infusion of angiotensin also led to an increased urinary eliminiation of prostaglandin E. These results show that urinary prostaglandins may originate from the kidney, indicating that renally synthesized prostaglandins diffuse or are excreted into the tubule. Thus, urinary prostaglandins are a reflection of renal prostaglandin synthesis and have potential as a tool to delineate renal prostaglandin physiology and pathology.
Effect of hysterectomy on anorectal and urethrovesical physiology.
Authors: A Prior, K Stanley, A R Smith, N W Read
Journal: Gut (1992)

To investigate whether vaginal or total abdominal hysterectomy is associated with changes in anorectal and urethrovesical physiology, 26 women were studied before operation and six weeks and six months afterwards. The results showed a postoperative increase in both rectal and vesical sensitivity (p less than 0.01). Similar results were observed irrespective of the type of hysterectomy. No significant changes in rectal or bladder compliance were noted, and anal pressure and urethral pressure and length were unchanged after surgery. Whole gut transit was not affected by hysterectomy. Urinary symptoms occurred de novo in 6/26 women and gastrointestinal symptoms in 2/26 women. These results show that significant changes in rectal and vesical sensitivity occur after hysterectomy for benign disease. These persist for at least six months postoperatively but are not always associated with development of urinary or gastrointestinal symptoms.
Duration of High-Dose Interferon Alfa-2b Regimen for Resected High-Risk Melanoma
Authors: Sanjiv S. Agarwala, Robert J. Gray, Michael K.K. Wong
Journal: Journal of Clinical Oncology (2009)

HDI actually utilized. The induction therapy dose was 15 10 6 U/m 2 /d intravenously (IV) for 5 of 7 days for 4 weeks, whereas the standard HDI dose on the ECOG trials is 20 10 6 U/m 2 /d. This was followed by a flat dose of 10 10 6 U subcutaneously (SC) 3 times per week for 48 weeks (as compared to the standard HDI dose of 10 10 6 U/m 2 3 times per week for 48 weeks). Even if one allowed for dose reductions during the induction phase of the ECOG studies to match the lower prescribed dose on the Hellenic trial, the maintenance-phase dose is problematic. The latter has already been shown to be ineffective compared with observation in a large randomized European Organisation for Research and Treatment of Cancer trial (18952) 6 where 10 10 6 U administered SC for 1 year was found to be no better than observation alone. In effect, this nullifies any effect of the SC maintenance phase of the Hellenic trial and reduces this study to a comparison of “induction versus induction,” with all the additional caveats previously discussed. Since adjuvant therapy is given with curative intent, any change in its administration can have significant impact on patients. It is our contention, therefore, that the results of the Hellenic trial cannot and should not be considered conclusive and that the 1-year HDI regimen remain the standard of care for patients with high-risk melanoma as defined in the ECOG trials. The ongoing, high-priority ECOG 1697 trial we are conducting is randomly assigning 1,420 patients with intermediate- and high-risk melanoma to 1 month of IV induction at full standard dosages or to observation, and will shed more light on the issue of whether the induction therapy alone is sufficient for patients in the adjuvant setting.
Allergic Rhinitis (AR) and its Impact on Cost, Productivity and Healthcare Resource Use of Patients
Authors: Y.S. Punekar, R.D. O'Connor
Journal: Journal of Allergy and Clinical Immunology (2006)

RATIONALE: AR, although not associated with mortality or severe morbidity, exerts a significant burden on society due to its high prevalence and associated cost of treatment. Therefore, we estimated the impact of AR on cost, productivity and healthcare resource use of patients.METHODS: 476 AR patients along with their primary care physician (PCP) or allergy specialists (AS) provided information about annual physician visits and associated consultation time, cost of AR medications (in US dollars), and days missed from school/work/leisure activities. This burden was assessed for the entire cohort before comparing it between seasonal and perennial AR patients.RESULTS: 33% patients had 3 or more AR related physician visits in the previous year. The mean consultation time was 20.8 minutes (SE=0.77). The mean spending by patients for AR medications including co-payments was $31.79 during the previous month with 20% spending $50 or more. 37% of patients missed at least one day of work/school whereas 49% of retired patients missed at least one day of leisure activity due to AR in the previous year. This burden was comparable between seasonal and perennial AR patients.CONCLUSIONS: AR presents a significant impact on cost, productivity and healthcare resource use of patients and, this impact is comparable between seasonal and perennial AR patients. RATIONALE: AR, although not associated with mortality or severe morbidity, exerts a significant burden on society due to its high prevalence and associated cost of treatment. Therefore, we estimated the impact of AR on cost, productivity and healthcare resource use of patients. METHODS: 476 AR patients along with their primary care physician (PCP) or allergy specialists (AS) provided information about annual physician visits and associated consultation time, cost of AR medications (in US dollars), and days missed from school/work/leisure activities. This burden was assessed for the entire cohort before comparing it between seasonal and perennial AR patients. RESULTS: 33% patients had 3 or more AR related physician visits in the previous year. The mean consultation time was 20.8 minutes (SE=0.77). The mean spending by patients for AR medications including co-payments was $31.79 during the previous month with 20% spending $50 or more. 37% of patients missed at least one day of work/school whereas 49% of retired patients missed at least one day of leisure activity due to AR in the previous year. This burden was comparable between seasonal and perennial AR patients. CONCLUSIONS: AR presents a significant impact on cost, productivity and healthcare resource use of patients and, this impact is comparable between seasonal and perennial AR patients.
Positron Emission Tomography Reporter Genes and Reporter Probes: Gene and Cell Therapy Applications
Authors: Shahriar S. Yaghoubi, Dean O. Campbell, Caius G. Radu, Johannes Czernin
Journal: Theranostics (2012)

Positron emission tomography (PET) imaging reporter genes (IRGs) and PET reporter probes (PRPs) are amongst the most valuable tools for gene and cell therapy. PET IRGs/PRPs can be used to non-invasively monitor all aspects of the kinetics of therapeutic transgenes and cells in all types of living mammals. This technology is generalizable and can allow long-term kinetics monitoring. In gene therapy, PET IRGs/PRPs can be used for whole-body imaging of therapeutic transgene expression, monitoring variations in the magnitude of transgene expression over time. In cell or cellular gene therapy, PET IRGs/PRPs can be used for whole-body monitoring of therapeutic cell locations, quantity at all locations, survival and proliferation over time and also possibly changes in characteristics or function over time. In this review, we have classified PET IRGs/PRPs into two groups based on the source from which they were derived: human or non-human. This classification addresses the important concern of potential immunogenicity in humans, which is important for expansion of PET IRG imaging in clinical trials. We have then discussed the application of this technology in gene/cell therapy and described its use in these fields, including a summary of using PET IRGs/PRPs in gene and cell therapy clinical trials. This review concludes with a discussion of the future direction of PET IRGs/PRPs and recommends cell and gene therapists collaborate with molecular imaging experts early in their investigations to choose a PET IRG/PRP system suitable for progression into clinical trials.
Inherited structural polymorphism in human C2: evidence for genetic linkage between C2 and Bf.
Authors: C A Alper
Journal: The Journal of Experimental Medicine (1976)

Structural variation in the second component of human complement was identified in about 4% of serum samples from random unrelated individuals of all the major races. Three forms of C2 have been identified by isoelectric focusing in polyacrylamide gel and development of patterns in agarose gel containing antibody-sensitized sheep red cells and C2-deficient serum: C2 C (common), C2 A (acidic), and C2 B (basic). The C2 variants were shown to be inherited as autosomal codominant traits, and suggestive evidence for close linkage between C2 and Bf was obtained.
Changes in the influence of lymphoma- and HIV-specific factors on outcomes in AIDS-related non-Hodgkin lymphoma
Authors: S.K. Barta, M.S. Samuel, X. Xue, D. Wang, J.Y. Lee, N. Mounier, J.-M. Ribera, M. Spina, U. Tirelli, R. Weiss, L. Galicier, F. Boue, R.F. Little, K. Dunleavy, W.H. Wilson, C. Wyen, S.C. Remick, L.D. Kaplan, L. Ratner, A. Noy, J.A. Sparano
Journal: Annals of Oncology (2015)
Probiotics in inflamatory bowel disease
Authors: F Shanahan
Journal: Gut (2001)

Probiotics are live micro-organisms that alter the enteric microflora and have a beneficial effect on health. Bacteria associated with probiotic activity have frequently been lactobacilli or bifidobacteria, but Escherichia coli and enterococcal strains have been used, as have non-bacterial organisms such as Saccharomyces boulardii .

The rationale for using probiotics in inflammatory bowel disease (IBD) is based on persuasive evidence implicating intestinal bacteria in the pathogenesis of IBD.1 2 The most compelling evidence is derived from animal models; despite great diversity in genetic defects and immunopathology, a consistent feature is dependency on the presence of normal enteric flora for full expression of disease. It appears that the pathogenesis of IBD, particularly Crohn's disease, involves genetically influenced dysregulation of the mucosal immune …
Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria
Authors: Marc H. Jansen, Sophie E. Veldhuijzen van Zanten, Esther Sanchez Aliaga, Martijn W. Heymans, Monika Warmuth-Metz, Darren Hargrave, Erica J. van der Hoeven, Corrie E. Gidding, Eveline S. de Bont, Omid S. Eshghi, Roel Reddingius, Cacha M. Peeters, Antoinette Y.N. Schouten-van Meeteren, Rob H.J. Gooskens, Bernd Granzen, Gabriel M. Paardekooper, Geert O. Janssens, David P. Noske, Frederik Barkhof, Christof M. Kramm, W. Peter Vandertop, Gertjan J. Kaspers, Dannis G. van Vuurden
Journal: Neuro-Oncology (2014)

Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed. A multicenter retrospective cohort study was performed in the Netherlands, the UK, and Germany with central review of clinical data and MRI scans of children with DIPG. Cox proportional hazards with backward regression was used to select prognostic variables (P < .05) to predict the accumulated 12-month risk of death. These predictors were transformed into a practical risk score. The model's performance was validated by bootstrapping techniques. A total of 316 patients were included. The median overall survival was 10 months. Multivariate Cox analysis yielded 5 prognostic variables of which the coefficients were included in the risk score. Age ≤3 years, longer symptom duration at diagnosis, and use of oral and intravenous chemotherapy were favorable predictors, while ring enhancement on MRI at diagnosis was an unfavorable predictor. With increasing risk score categories, overall survival decreased significantly. The model can distinguish between patients with very short, average, and increased overall survival (medians of 7.0, 9.7, and 13.7 mo, respectively). The area under the receiver operating characteristic curve was 0.68. We developed a DIPG survival prediction tool that can be used to predict the outcome of patients and for stratification in trials. Validation of the model is needed in a prospective cohort.
Narrowing social inequalities in health? Analysis of trends in mortality among babies of lone mothers
Authors: M. Whitehead, F. Drever
Journal: BMJ (1999)

To examine trends in mortality among babies registered solely by their mother (lone mothers) and to compare these with trends in infant mortality for couple registrations overall and couple registrations subdivided by social class of father.Analysis of trends in infant death rates from 1975 to 1996 for the three groups. The data source was the national linked infant mortality file, containing all records of infant death in England and Wales linked to the respective birth records.England and Wales.All live births (n=14.3 million) from 1975 to 1996; all deaths of infants from birth to 12 months of age over the same period (n=135 800).Death rates in the perinatal, neonatal, and postneonatal periods and for infancy overall.For the babies of lone mothers infant mortality has fallen to less than a third of the 1975 level, with a clear reduction in the gap between the mortality in these babies compared with all couple registrations: the excess mortality in solely registered births was 79% in 1975 reducing to 33% in 1996. Most of the narrowing of the sole-couple differential was associated with the neonatal period, for which there is now no appreciable gap. For couple registrations analysed by social class of father, infant death rates have more than halved in each social class from 1975 to 1996. The reductions in mortality were greater in the late 1970s and early 1990s. Infant death rates in classes IV-V remained between 50% and 65% higher than in classes I-II. Differentials between social classes were largest in the postneonatal period and smallest in the perinatal and neonatal periods. The gap in perinatal and neonatal mortality between the babies of lone mothers and couple parents in social classes IV-V has disappeared.The differential in infant mortality between social classes still exists, whereas the differential between sole and couple registrations has decreased, showing positive progress in the reduction of inequalities. As the reduction in the differential was confined to the neonatal period these improvements may be more a reflection of healthcare factors than of factors associated with lone mothers' social and economic circumstances.
Forced oscillations in the clinical setting in young children with neonatal lung disease
Authors: K. Udomittipong, P. D. Sly, H. J. Patterson, C. L. Gangell, S. M. Stick, G. L. Hall
Journal: European Respiratory Journal (2008)

The extent of respiratory dysfunction is not well characterised in children with neonatal chronic lung disease (nCLD) too young to perform spirometry. Forced oscillations are easily performed by healthy young children; however, they may be more difficult for those with nCLD. The present study aimed to describe the feasibility of using the forced oscillation technique in children with nCLD in a routine clinical setting and to investigate the influence of neonatal factors on subsequent lung function. Respiratory function tests were attempted in 64 patients with nCLD aged 3.2–6.6 yrs. Respiratory resistance and reactance at 6, 8 and 10 Hz were expressed as z-scores derived from a healthy reference population. The within-test variation and between-test repeatability were also assessed. Technically, satisfactory data were obtained from 77% of children. On grouped data, z-scores for all oscillatory indices were different from zero and related to hospital oxygen administration in the neonatal period. In conclusion, the forced oscillation technique was feasible in preschool children with neonatal chronic lung disease in the clinical outpatient setting. These children had lung function significantly worse than that predicted from healthy children. Respiratory function assessed using forced oscillations appeared to reflect the severity of lung disease during the neonatal period.