tbuckley/cabot-search huggingface dataset:
Studies on high molecular weight renin from hog kidney.
Authors: M Levine, K E Lentz, J R Kahn, F E Dorer, L T Skeeggs
Journal: Circulation Research (1978)

Previous reports by several investigators on the activation of a high molecular weight renin have not been confirmed.A simple method of extracting hog kidneys by using toluene was modified to yield partially purified renin with a molecular weight of 60,000, exclusively.Attempts to increase the activity of this renin by acidification resulted in a loss of 20-90% of the total activity, although the renin activity remaining was converted to a molecular weight of 40,000 and its specific activity increased 10-fold over that of the original.Attempts to obtain increased activity of the 60,000 molecular weight renin by adding crude kidney extract before the acidification did not result in activation.Activity of renin partially purified by a procedure involving acidification was inhibited by the addition of crude kidney extract.Incubation of increasing amounts of crude kidney extract alone resulted in a progressive reduction in angfotensin produced.When the angiotensin curve was extrapolated to zero extract concentration, (be level of renin activity was twice as great as that found after acidification of such crude extracts.The high angiotensinase activity of the crude extract was partially inhibited by EDTA, but in the presence of the latter, diisopropylfluoropbosphate and phenylmethanesulfonyl fluoride, alone or together, gave no added protection.The significance of the high molecular weight renin in such extracts is not clear, although it is apparent that it is not a less active precursor of renin, as has been suggested by some investigators.SINCE THE original observation by Lumbers' that renin in amniotic fluid is activated by acidification, and Rubin's account of similar activation in extracts of lyophilized hog kidney, 2 there have been a number of reports of renin activation in amniotic fluids, 3 "* kidney extracts,*" 9 uterus, 10 and plasma. 1 -•'• 5 ' "~1 7 In several cases, it was determined that the renin which underwent activation had a molecular weight higher than normal. 6~8> l0 -17 Day et al.* reported that both of two samples of amniotic fluid they investigated by gel filtration had high molecular weight renin, although they found varying amounts of inactive high molecular weight renin in the plasma of only 11 of 28 patients tested, and none at all in normal control subjects.However, Skinner et a\. 4 found that inactive renin in the plasma of all their patients and normal control subjects was activated by acidification, and Derkx et al. 1 * and Boyd 16 reported similar findings for almost all of their patients.Boyd also noted that the molecular weight of
Differential anti‐inflammatory effects of large and small particle size inhaled corticosteroids in asthma
Authors: D. Menzies, A. Nair, P. Hopkinson, L. McFarlane, B. J. Lipworth
Journal: Allergy (2007)

Background: Extra‐fine particle formulations of hydrofluoroalkane‐134a beclometasone dipropionate (HFA‐BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC‐BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA‐BDP and CFC‐BDP on pulmonary and systemic markers of asthmatic inflammation. Methods: A double‐blind randomized crossover trial was undertaken comparing the anti‐inflammatory effects of HFA‐BDP (100 and 400 μ g/day) and CFC‐BDP (200 and 800 μ g/day). Treatment with montelukast was evaluated as add‐on to the higher dose of BDP. Results: Compared with baseline after withdrawal of usual asthma therapy, 100 μ g of HFA‐BDP significantly attenuated serum eosinophilic cationic protein levels (0.61‐fold change, 95% CI 0.49–0.77; a 39% reduction, P &lt; 0.001), but 200 μ g of CFC‐BDP did not (0.87‐fold change, 95% CI 0.63–1.23; P = 1). A dose of 800 μ g of CFC‐BDP and 400 μ g of HFA‐BDP led to reductions in exhaled nitric oxide (0.57‐fold change, 95% CI 0.44–0.73; a 43% reduction, P &lt; 0.001 and 0.65‐fold change, 95% CI 0.47–0.91; a 35% reduction, P = 0.008, respectively); and peripheral eosinophils (−74 cells/ μ l, 95% CI −146 to −2; P = 0.020 and −77 cells/ μ l, 95% CI −140 to −14; P = 0.012, respectively). Montelukast further reduced exhaled nitric oxide (0.81‐fold change, 95% CI 0.66–0.98; P = 0.028) with 400 μ g HFA‐BDP and eosinophils (−44 cells/ μ l, 95% CI −80 to −8; P = 0.012) with 800 μ g CFC‐BDP, but not vice versa. Conclusion: Chlorofluorocarbon beclometasone dipropionate and HFA‐BDP have differential effects on pulmonary and systemic inflammation, which dictate the additive effects of montelukast.
Associations between MRI-defined synovitis, bone marrow lesions and structural features and measures of pain and physical function in hand osteoarthritis
Authors: Ida Kristin Haugen, Pernille Bøyesen, Barbara Slatkowsky-Christensen, Sølve Sesseng, Désirée van der Heijde, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> To explore associations between MRI features and measures of pain and physical function in hand osteoarthritis (OA). <h3>Methods</h3> Eighty-five patients (77 women) with mean (SD) age of 68.8 (5.6) years underwent contrast-enhanced MRI of the interphalangeal joints (dominant hand) and clinical joint assessment. One investigator read the MRIs for presence/severity of osteophytes, joint space narrowing, erosions, bone attrition, cysts, malalignment, synovitis, flexor tenosynovitis, bone marrow lesions (BMLs) and ligament discontinuity according to the proposed Oslo hand OA MRI score. Pain and physical function were assessed by joint palpation (tenderness yes/no), self-reported questionnaires (Australian/Canadian (AUSCAN) hand index, Functional Index of hand osteoarthritis (FIHOA), Arthritis Impact Measurement Scale-2 (AIMS-2) hand/finger) and grip strength. Logistic regression with generalised estimating equations was used to explore associations between the presence of MRI features and joint tenderness, and linear regression for associations between the burden of MRI abnormalities and patient-reported outcomes and grip strength (adjusted for age and sex). MRI features with p&lt;0.25 were introduced into a multivariate model. The final model included features with p≤0.10 (backward selection). <h3>Results</h3> MRI-defined moderate/severe synovitis (OR=2.4; p&lt;0.001), BMLs (OR=1.5; p=0.06), erosions (OR=1.4; p=0.05), attrition (OR=2.5; p&lt;0.001) and osteophytes (OR=1.4; p=0.10) were associated with joint tenderness independently of each other (final model adjusted for age and sex). The sum score of MRI-defined attrition was associated with FIHOA (B=0.58; p=0.005), while the sum score of osteophytes was associated with grip strength (B=−0.39; p&lt;0.001). No significant associations were found with AUSCAN pain/physical function or AIMS-2 hand/finger subscales. <h3>Conclusion</h3> MRI-defined synovitis, BMLs, erosions and attrition were associated with joint tenderness. Synovitis and BMLs may be targets for therapeutic interventions in hand OA.
Hot biopsy for right colonic polypectomy: an audit of practice and complications in a large teaching hospital
Authors: T. Raine, G. Corbett, E. Cameron
Journal: Gut (2011)

<h3>Introduction</h3> Evidence to guide the selection of techniques for colonoscopic polypectomy remains limited and confusing. Limited evidence suggests that monopolar hot biopsy is associated with an increased risk of postpolypectomy bleeding1 and an increased risk of perforation when used in the right colon.2 Although no clear consensus exists on this topic, a guidance statement endorsed by the British Society of Gastroenterology3 recommended the use of cold snare for small sessile polyps in the right colon, with hot snare used only for larger sessile polyps or pedunculated polyps. The American Society of Gastrointestinal Endoscopy and the American College of Gastroenterologists have also advised caution in the use of hot biopsy in the right colon.45 Nevertheless, clinical practice remains varied and inconsistent.6 <h3>Methods</h3> The authors interrogated the electronic endoscopy database in our large teaching hospital for information about all colonoscopies performed during a 12-month period. Whenever a polypectomy was recorded, information regarding polyp size, location and method of removal was correlated with histological results and records of complications. Hot biopsies were performed using standardised diathermy settings (Erbe ICC 200, forced coagulation 30 W). <h3>Results</h3> A total of 3925 colonoscopies were performed during the 12-month period by 44 endoscopists, including 31 trainees. At least one polypectomy was performed in 1399 patients (36%), and a total of 1463 adenomas were removed from 851 patients (overall adenoma detection rate 21.6%). 1255 polypectomies were performed using hot biopsy; 422 (34%) of these were in the right colon, of which 235 were adenomas and 187 hyperplastic polyps. Removal by hot biopsy accounted for 38% of all right sided adenomas. A single perforation occurred in this series, during resection of an 18 mm pedunculated sigmoid polyp. There were no complications with hot biopsy, giving a perforation rate for hot biopsy in the right colon of 0% (95% CI 0% to 0.66%). <h3>Conclusion</h3> Despite fears about safety, hot biopsy in the right colon continues to be frequently practiced. This was associated with no perforations in this large series. However, 44% of lesions removed from the right colon by this technique were hyperplastic polyps. With such a high rate of non-neoplastic lesions, any technique associated with even a small increased risk of perforation requires careful justification. Further data are required to define the safety and role of hot biopsy in the right colon.
Role of hypoxia on increased blood pressure in patients with obstructive sleep apnoea.
Authors: S Okabe, W Hida, Y Kikuchi, O Taguchi, H Ogawa, A Mizusawa, H Miki, K Shirato
Journal: Thorax (1995)

BACKGROUND--Cyclical changes in systemic blood pressure occur during apnoeic episodes in patients with obstructive sleep apnoea (OSA). Although several factors including arterial hypoxaemia, intrathoracic pressure changes, and disruption of sleep architecture have been reported to be responsible for these changes in blood pressure, the relative importance of each factor remains unclear. This study assessed the role of hypoxaemia on the increase in blood pressure during apnoeic episodes. METHODS--The blood pressure in apnoeic episodes during sleep and the blood pressure response to isocapnic intermittent hypoxia whilst awake were measured in 10 men with OSA. While asleep the blood pressure was measured non-invasively using a Finapres blood pressure monitor with polysomnography. The response of the blood pressure to hypoxia whilst awake was also measured while the subjects intermittently breathed a hypoxic (5% or 7% oxygen) gas mixture. Each hypoxic gas exposure was continued until a nadir arterial oxygen saturation (nSaO2) of less than 75% was reached, or for a period of 100 seconds. The exposure was repeated five times in succession with five interposed breaths of room air in each run. RESULTS--The mean (SD) increase in blood pressure (delta MBP) during apnoeic episodes was 42.1 (17.3) mm Hg during rapid eye movement (REM) sleep and 31.9 (12.5) mm Hg during non-REM sleep. The delta MBP during apnoeic episodes showed a correlation with the decrease of nSaO2 (delta SaO2) (r2 = 0.30). The change in blood pressure in response to intermittent hypoxia whilst awake was cyclical and qualitatively similar to that during apnoeic episodes. Averaged delta MBP at an SaO2 of 7% and 5% oxygen was 12.6 (5.7) and 13.4 (3.6) mm Hg, respectively, whereas the averaged delta MBP at the same delta SaO2 during apnoeic episodes was 38.4 (15.5) and 45.2 (20.5) mm Hg, respectively. CONCLUSIONS--The blood pressure response to desaturation whilst awake was about one third of that during apnoeic episodes. These results suggest that factors other than hypoxia may play an important part in raising the blood pressure during obstructive sleep apnoea.
Functions of Notch Signaling in the Immune System: Consensus and Controversies
Authors: Julie S. Yuan, Philaretos C. Kousis, Sara Suliman, Ioana Visan, Cynthia J. Guidos
Journal: Annual Review of Immunology (2010)

Mammalian genomes encode up to four Notch receptors (Notch1–4) and five Notch ligands of the DSL (Delta/Serrate/Lag-2) family, and Notch signaling controls a wide spectrum of developmental processes. Intrathymic Notch1 signaling is essential for several distinct aspects of early T cell development. Notch signaling has also been implicated as a key regulator of peripheral T cell activation and effector cell differentiation, but its functions in these processes remain poorly understood. Notch signaling is dispensable for B cell development in the bone marrow, but it is required to generate the innate-like marginal zone B cell subset in the spleen and may also regulate plasma cell functions. Modification of Notch receptors by fringe glycosyltransferases influences many Notch-dependent aspects of hematopoiesis by altering Notch responsiveness to Delta-like versus Jagged DSL ligands. Here we review recent advances in general aspects of Notch signaling, as well as studies probing Notch functions in these immunological processes.
Interferons Regulate the Phenotype of Wild-type and Mutant Herpes Simplex Viruses In Vivo
Authors: David A. Leib, Travis E. Harrison, Kathleen M. Laslo, Michael A. Machalek, Nathaniel J. Moorman, Herbert W. Virgin
Journal: The Journal of Experimental Medicine (1999)

Mechanisms responsible for neuroattenuation of herpes simplex virus (HSV) have been defined previously by studies of mutant viruses in cultured cells. The hypothesis that null mutations in host genes can override the attenuated phenotype of null mutations in certain viral genes was tested. Mutants such as those in infected cell protein (ICP) 0, thymidine kinase, ribonucleotide reductase, virion host shutoff, and ICP34.5 are reduced in their capacity to replicate in nondividing cells in culture and in vivo. The replication of these viruses was examined in eyes and trigeminal ganglia for 1–7 d after corneal inoculation in mice with null mutations (−/−) in interferon receptors (IFNR) for type I IFNs (IFN-α/βR), type II IFN (IFN-γR), and both type I and type II IFNs (IFN-α/β/γR). Viral titers in eyes and ganglia of IFN-γR−/− mice were not significantly different from congenic controls. However, in IFN-α/βR−/− or IFN-α/β/γR−/− mice, growth of all mutants, including those with significantly impaired growth in cell culture, was enhanced by up to 1,000-fold in eyes and trigeminal ganglia. Blepharitis and clinical signs of infection were evident in IFN-α/βR−/− and IFN-α/β/γR−/− but not control mice for all viruses. Also, IFNs were shown to significantly reduce productive infection of, and spread from intact, but not scarified, corneas. Particularly striking was restoration of near-normal trigeminal ganglion replication and neurovirulence of an ICP34.5 mutant in IFN-α/βR−/− mice. These data show that IFNs play a major role in limiting mutant and wild-type HSV replication in the cornea and in the nervous system. In addition, the in vivo target of ICP34.5 may be host IFN responses. These experiments demonstrate an unsuspected role for host factors in defining the phenotypes of some HSV mutants in vivo. The phenotypes of mutant viruses therefore cannot be interpreted based solely upon studies in cell culture but must be considered carefully in the context of host factors that may define the in vivo phenotype.
Reference ranges for interrupter resistance technique: the Asthma UK Initiative
Authors: P.J.F.M. Merkus, J. Stocks, N. Beydon, E. Lombardi, M. Jones, S.A. Mckenzie, J. Kivastik, B.G.M. Arets, S. Stanojevic
Journal: European Respiratory Journal (2009)

Measuring interrupter resistance ( R int ) is an increasingly popular lung function technique and especially suitable for preschool children because it is simple, quick and requires only passive cooperation. A European Respiratory Society (ERS)/American Thoracic Society (ATS) Task Force recently published empirical recommendations related to procedures, limitations and interpretation of the technique. However, for valid interpretation, high-quality reference equations are required and these have been lacking. The aim of the present study was to collate R int data from healthy children in order to produce more robust reference equations. A further aim was to examine the influence of methodological differences on predicted R int values. R int data from healthy children were collected from published and unpublished sources. Reference equations for expiratory and inspiratory R int were developed using the LMS (lambda, mu, sigma) method. Data from 1,090 children (51% males) aged 3–13 yrs were collated to construct sex-specific reference equations for expiratory R int and data from 629 children (51% males) were collated for inspiratory R int . Height was the best independent predictor of both expiratory and inspiratory R int . Differences between centres were clinically irrelevant, and differences between ethnic groups could not be examined. The availability of a large and generalisable sample and the use of modern statistical techniques enabled the development of more appropriate reference equations for R int in young children.
Thrombin-Receptor Antagonist Vorapaxar in Acute Coronary Syndromes
Authors: Pierluigi Tricoci, Zhen Huang, Claes Held, David J. Moliterno, Paul W. Armstrong, Frans Van de Werf, Harvey D. White, Philip E. Aylward, Lars Wallentin, Edmond Chen, Yuliya Lokhnygina, Jinglan Pei, Sergio Leonardi, Tyrus L. Rorick, Ann M. Kilian, Lisa H.K. Jennings, Giuseppe Ambrosio, Christoph Bode, Angel Cequier, Jan H. Cornel, Rafael Diaz, Aycan Erkan, Kurt Huber, Michael P. Hudson, Lixin Jiang, J. Wouter Jukema, Basil S. Lewis, A. Michael Lincoff, Gilles Montalescot, José Carlos Nicolau, Hisao Ogawa, Matthias Pfisterer, Juan Carlos Prieto, Witold Ruzyllo, Peter R. Sinnaeve, Robert F. Storey, Marco Valgimigli, David J. Whellan, Petr Widimsky, John Strony, Robert A. Harrington, Kenneth W. Mahaffey
Journal: New England Journal of Medicine (2011)

Vorapaxar is a new oral protease-activated-receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation.In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization.Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (Kaplan-Meier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P=0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P=0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups.In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.).
A Prospective Study of Hyperparathyroidism in Individuals Exposed to Radiation in Childhood
Authors: Joel Cohen
Journal: JAMA (1990)

To determine the effects of childhood irradiation on the parathyroid glands, a cohort of 4297 patients who received radiation to the tonsils before the age of 16 years has been followed-up prospectively. Among the 2923 patients who were located and provided information, 32 patients developed clinical hyperparathyroidism. The incidence of clinical hyperparathyroidism was 18.7 per 100,000 person-years below the age of 40 years and 171 per 100,000 person-years in the age range of 40 to 60 years. This represents a 2.9-fold (95% confidence interval, 1.6 to 4.3) and 2.5-fold (95% confidence interval, 1.1 to 3.9) increase in the incidence of hyperparathyroidism compared with that among the general population. In addition, 31% of the patients who developed hyperparathyroidism also developed thyroid cancer, which is higher than the 11.2% prevalence of thyroid cancer in the patients who received radiation therapy who did not develop parathyroid tumors. Patients with a history of head and neck irradiation should have their parathyroid glands evaluated on a regular basis.
International Olympic Committee consensus statement on the health and fitness of young people through physical activity and sport
Authors: Margo Mountjoy, Lars Bo Andersen, Neil Armstrong, Stuart Biddle, Colin Boreham, Hans-Peter Brandl Bedenbeck, Ulf Ekelund, Lars Engebretsen, Ken Hardman, Andrew Hills, Sonja Kahlmeier, Susi Kriemler, Estelle Lambert, Arne Ljungqvist, Victor Matsudo, Heather McKay, Lyle Micheli, Russell Pate, Chris Riddoch, Patrick Schamasch, Carl Johan Sundberg, Grant Tomkinson, Esther van Sluijs, Willem van Mechelen
Journal: British Journal of Sports Medicine (2011)

Lung cancer is the most frequent malignant neoplasm in most countries, and the main cancer-related cause of mortality worldwide in both sexes combined. The geographic and temporal patterns of lung cancer incidence, as well as lung cancer mortality, on a population level are chiefly determined by tobacco consumption, the main aetiological factor in lung carcinogenesis. Other factors such as genetic susceptibility, poor diet, occupational exposures and air pollution may act independently or in concert with tobacco smoking in shaping the descriptive epidemiology of lung cancer. Moreover, novel approaches in the classification of lung cancer based on molecular techniques have started to bring new insights to its aetiology, in particular among nonsmokers. Despite the success in delineation of tobacco smoking as the major risk factor for lung cancer, this highly preventable disease remains among the most common and most lethal cancers globally. Future preventive efforts and research need to focus on non-cigarette tobacco smoking products, as well as better understanding of risk factors underlying lung carcinogenesis in never-smokers.