tbuckley/cabot-search huggingface dataset:
In vitro release of neutrophil elastase, myeloperoxidase and beta-glucuronidase in patients with emphysema and healthy subjects
Authors: TE Renkema, DS Postma, JA Noordhoek, HJ Sluiter, HF Kauffman
Journal: European Respiratory Journal (1991)

Evidence is accumulating that cigarette smoking plays an important role in the protease-antiprotease imbalance in alpha 1-antitrypsin-sufficient emphysema. Since most smokers, however, do not develop emphysema, it has to be presumed that other factors in addition to smoking contribute to the origin of the imbalance. The major source of proteases is the polymorphonuclear leucocyte (PMN). We tested the hypothesis that an abnormality in the releasability of PMN might predispose for the development of emphysema. Therefore, the release of elastase, myeloperoxidase, and beta-glucuronidase from PMN was investigated in patients with emphysema and healthy controls, matched for sex, age, and smoking habits. PMN were isolated from peripheral blood and stimulated with calcium-ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), and serum-treated zymosan (STZ). Total enzyme content of PMN was measured after cell lysis with Triton X-100. Total elastase, myeloperoxidase, and beta-glucuronidase content of PMN were not significantly different in healthy subjects and patients with emphysema. In vitro release of elastase and myeloperoxidase from both stimulated and unstimulated PMN was not significantly different in healthy subjects and emphysematous patients. Moreover, no differences were found between smoking and ex-smoking individuals. Beta-glucuronidase release tended to be lower in patients with emphysema than in healthy controls. We conclude that an abnormality in the releasability of peripheral PMN is unlikely to be a pathogenetic factor in emphysema.
Preventing TB in patients with Crohn's disease needing infliximab or other anti-TNF therapy
Authors: D S Rampton
Journal: Gut (2005)

In patients with Crohn’s disease, the increased risk of active tuberculosis (TB) associated with infliximab makes it necessary to screen for active and latent TB before this or other anti-tumour necrosis factor treatment is begun. This paper outlines how such screening should be undertaken, and how to decide which patients need antituberculous treatment or chemoprophylaxis before infliximab.

The increased risk of active tuberculosis (TB) associated with infliximab makes necessary a screen for active and latent TB before this or other anti-tumour necrosis factor (TNF) treatment is begun in patients with Crohn’s disease. This paper outlines how such screening should be undertaken, and how to decide which patients need antituberculous treatment or chemoprophylaxis before infliximab. All patients need a careful history for TB and a chest x ray. The minority of patients with a history of TB or an abnormal chest x ray should be referred for assessment by a TB specialist. Of the remainder, those with Crohn’s disease who are on immunosuppressive therapy do not require tuberculin testing. Comparison of their risk of TB while on anti-TNF therapy with the risks of chemoprophylaxis induced hepatitis indicates that black Africans aged over 15 years, South Asians born outside the UK, and other ethnic groups resident in the UK for less than five years should be considered for chemoprophylaxis with isoniazid for six months. For how to minimise the risk of TB in the small minority of patients with inflammatory bowel disease not on immunosuppressive treatment, readers are referred to the more detailed guidelines published in Thorax .1

Infliximab is of proven benefit in the treatment of chronic active Crohn’s disease2 as well as in rheumatoid arthritis3 and ankylosing spondylitis4; preliminary data suggest it may also have a therapeutic role in refractory active ulcerative colitis.5–7 …
IL-2 coordinates IL-2–producing and regulatory T cell interplay
Authors: Inês F. Amado, Julien Berges, Rita J. Luther, Marie-Pierre Mailhé, Sylvie Garcia, Antonio Bandeira, Casey Weaver, Adrian Liston, Antonio A. Freitas
Journal: The Journal of Experimental Medicine (2013)

Many species of bacteria use quorum sensing to sense the amount of secreted metabolites and to adapt their growth according to their population density. We asked whether similar mechanisms would operate in lymphocyte homeostasis. We investigated the regulation of the size of interleukin-2 (IL-2)–producing CD4+ T cell (IL-2p) pool using different IL-2 reporter mice. We found that in the absence of either IL-2 or regulatory CD4+ T (T reg) cells, the number of IL-2p cells increases. Administration of IL-2 decreases the number of cells of the IL-2p cell subset and, pertinently, abrogates their ability to produce IL-2 upon in vivo cognate stimulation, while increasing T reg cell numbers. We propose that control of the IL-2p cell numbers occurs via a quorum sensing–like feedback loop where the produced IL-2 is sensed by both the activated CD4+ T cell pool and by T reg cells, which reciprocally regulate cells of the IL-2p cell subset. In conclusion, IL-2 acts as a self-regulatory circuit integrating the homeostasis of activated and T reg cells as CD4+ T cells restrain their growth by monitoring IL-2 levels, thereby preventing uncontrolled responses and autoimmunity.
Nitric oxide and angiotensin II. Glomerular and tubular interaction in the rat.
Authors: L De Nicola, R C Blantz, F B Gabbai
Journal: Journal of Clinical Investigation (1992)

Nitric oxide (NO) has been proposed to modulate the renal response to protein as well as basal renal hemodynamics. We investigated whether NO and angiotensin II (AII) interact to control glomerular hemodynamics and absolute proximal tubular reabsorption (APR) during glycine infusion and in unstimulated conditions. In control rats, glycine increased single nephron GFR and plasma flow with no change in APR. The NO synthase blocker, NG-monomethyl L-arginine (LNMMA), abolished the vasodilatory response to glycine, possibly through activation of tubuloglomerular feedback due to a decrease in APR produced by LNMMA + glycine. Pretreatment with an AII receptor antagonist, DuP 753, normalized the response to glycine at both glomerular and tubular levels. In unstimulated conditions, LNMMA produced glomerular arteriolar vasoconstriction, decreased the glomerular ultrafiltration coefficient, and reduced single nephron GFR. These changes were associated with a striking decrease in APR. DuP 753 prevented both glomerular and tubular changes induced by LNMMA. In conclusion, NO represents a physiological antagonist of AII at both the glomerulus and tubule in both the basal state and during glycine infusion; and inhibition of NO apparently enhances or uncovers the inhibitory effect of AII on proximal reabsorption.
Applications to the social and clinical sciences
Authors: Horacio Fabrega, Jr.
Journal: Behavioral and Brain Sciences (2005)

Fully interpreted, Lewis's dynamic systems modeling of emotion encompasses psychological-adaptation thinking and individual and group differences in normal and abnormal behavior. It weakens the categorical perspective in evolutionary psychology and the clinical sciences; and suggests continuity between “normal” or “abnormal” behavior in whatever way this is self and culturally constituted, although culture/linguistic factors and selfhood are neglected. Application of a dynamic systems model could improve formulation of clinical problems.
Cost effectiveness analysis of antenatal HIV screening in United Kingdom
Authors: A E Ades, M J Sculpher, D M Gibb, R Gupta, J Ratcliffe
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To assess the cost effectiveness of universal antenatal HIV screening compared with selective screening in the United Kingdom. <b>Design:</b> Incremental cost effectiveness analysis relating additional costs of screening to life years gained. Maternal and paediatric costs and life years were combined. <b>Setting:</b> United Kingdom. <b>Main outcome measures:</b> Number of districts for which universal screening would be cost effective compared with selective screening under various conditions. <b>Results:</b> On base case assumptions, a new diagnosis of a pregnant woman with HIV results in a gain of 6.392 life years and additional expenditure of £14 833. If decision makers are prepared to pay up to £10 000 for an additional life year, this would imply a net benefit of £49 090 (range £12 300-£59 000), which would be available to detect each additional infected woman in an antenatal screening programme. In London, universal antenatal screening would be cost effective compared with a selective screening under any reasonable assumptions about screening costs. Outside London, universal screening with uptake above 90% would be cost effective with a £0.60 HIV antibody test cost and up to 3.5 minutes for pretest discussion. Cost effectiveness of universal testing is lower if selective testing can achieve high uptake among those at higher risk. A universal strategy with only 50% uptake may not be less cost effective in low prevalence districts and may cost more and be less effective than a well run selective strategy. <b>Conclusions:</b> Universal screening with pretest discussion should be adopted throughout the United Kingdom as part of routine antenatal care as long as test costs can be kept low and uptake high. <h3>Key messages</h3> In 1997 only 13% of undiagnosed HIV infection in pregnant women was picked up on antenatal testing, resulting in many preventable paediatric infections Assuming NHS willingness to pay £10 000 per life year gained, universal testing would be much more cost effective than selective testing throughout London on any reasonable assumptions on costs, prevalence, and uptake of testing Outside London, universal testing would also be cost effective, even allowing 2-4 minutes for pretest discussion, provided that test costs were no more than £0.60 and uptake exceeded 90% Low cost tests could be achieved by pooling antenatal sera or centralisation of testing Universal testing with uptake of 50% may be less cost effective than a well run selective programme
Letters Regarding Article by Patti et al, “Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) Study”
Authors: Pierluigi Tricoci, Robert A. Harrington, Marco Valgimigli
Journal: Circulation (2005)
CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection
Authors: Victor S. Cortez, Luisa Cervantes-Barragan, Christina Song, Susan Gilfillan, Keely G. McDonald, Roxane Tussiwand, Brian T. Edelson, Yoshinori Murakami, Kenneth M. Murphy, Rodney D. Newberry, L. David Sibley, Marco Colonna
Journal: The Journal of Experimental Medicine (2014)

Retention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. We find that both CD4+CD8+ and CD4+ T cells in the intestinal epithelium, as well as CD8+ T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule class I–restricted T cell–associated molecule (Crtam) upon activation, whereas the ligand of Crtam, cell adhesion molecule 1 (Cadm1), is expressed on gut CD103+DCs. Lack of Crtam–Cadm1 interactions in Crtam−/− and Cadm1−/− mice results in loss of CD4+CD8+ T cells, which arise from mucosal CD4+ T cells that acquire a CD8 lineage expression profile. After acute oral infection with Toxoplasma gondii, both WT and Crtam−/− mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam−/− mice. The almost exclusive TH1 response in Crtam−/− mice resulted in more efficient control of intestinal T. gondii infection. Thus, Crtam–Cadm1 interactions have a major impact on the residency and maintenance of CD4+CD8+ T cells in the gut mucosa in the steady state. During pathogenic infection, Crtam–Cadm1 interactions regulate the dynamic equilibrium between newly formed CD4+ T cells and their retention in the gut, thereby shaping representation of disparate CD4+ T cell subsets and the overall quality of the CD4+ T cell response.
Forced expiratory manoeuvres in children: do they meet ATS and ERS criteria for spirometry?
Authors: H.G.M. Arets, H.J.L. Brackel, C.K. van der Ent
Journal: European Respiratory Journal (2001)

The aim of this study was to evaluate the applicability of American Thoracic Society and European Respiratory Society criteria for spirometry in children. Maximal expiratory flow/volume (MEFV) measurements from 446 school-age children, experienced in performing MEFV manoeuvres, were studied and acceptability (start-of-test (backward extrapolated volume as a percentage of forced vital capacity (FVC) ([Vbc%FVC) or as an absolute value (Vbe), end-of-test (forced expiratory time (FET)) and reproducibility criteria (absolute and percentage difference between best and second-best FVC and forced expiratory volume in one second (FEV1) (deltaFVC, deltaFVC %, deltaFEV1 and deltaFEV1 %)) were applied to these manoeuvres. The Vbe%FVC criterion was met by 91.5%, the Vbe <0.15 L criterion by 94.8% and the Vbe <0.10 L by 60.1% of children. Vbe <0.15 L appeared to be a more useful parameter than Vbe%FVC. The FET criterion was met by only 15.3% of children. deltaFVC <0.2 L and deltaFEV1 <0.2 L were met by 97.1% and 98.4%, and deltaFVC <0.1 L and deltaFEV1 <0.1 L by 79.8% and 84.3% of the children, respectively. These criteria appeared to be less useful compared to percentage criteria (deltaFVC % and deltaFEV1 %). Even experienced children did not meet all international criteria for spirometry. However, most of their MEFV curves are useful for interpretation. Based on the performance of these children, a re-evaluation of criteria for maximal expiratory flow/volume measurements in children is proposed.
Randomized Trial of Intravenous Iron Supplementation in Patients With Chemotherapy-Related Anemia Without Iron Deficiency Treated With Darbepoetin Alfa
Authors: Paolo Pedrazzoli, Antonio Farris, Salvatore Del Prete, Filomena Del Gaizo, Daris Ferrari, Clara Bianchessi, Giuseppe Colucci, Alberto Desogus, Teresa Gamucci, Alessandro Pappalardo, Giuseppe Fornarini, Paola Pozzi, Alessandra Fabi, Roberto Labianca, Francesco Di Costanzo, Simona Secondino, Enrico Crucitta, Federica Apolloni, Antonio Del Santo, Salvatore Siena
Journal: Journal of Clinical Oncology (2008)

Unresponsiveness to erythropoiesis-stimulating agents, occurring in 30% to 50% of patients, is a major limitation to the treatment of chemotherapy-related anemia. We have prospectively evaluated whether intravenous iron can increase the proportion of patients with chemotherapy-related anemia who respond to darbepoetin.Between December 2004 and February 2006, 149 patients with lung, gynecologic, breast, and colorectal cancers and >or= 12 weeks of planned chemotherapy were enrolled from 33 institutions. Patients were required to have hemoglobin <or= 11 g/L and no absolute or functional iron deficiency. All patients received darbepoetin 150 microg subcutaneously once weekly for 12 weeks and were randomly assigned to sodium ferric gluconate 125 mg intravenously (IV) weekly for the first 6 weeks (n = 73) or no iron (n = 76). Primary end point of the study was the percentage of patients achieving hematopoietic response (hemoglobin >or= 12 g/dL or >or= 2 g/dL increase).Hematopoietic response by intention-to-treat analysis was 76.7% (95%CI, 65.4% to 85.8%) in the darbepoetin/iron group and 61.8% (95%CI, 50.0% to 72.7%) in the darbepoetin group (P = .0495). Among patients fulfilling eligibility criteria and having received at least four darbepoetin administrations, hematopoietic responses in the darbepoetin/iron group (n = 53) and in the darbepoetin-only group (n = 50) were 92.5% (95% CI, 81.8% to 97.9%) and 70% (95% CI, 55.4% to 82.1%), respectively (P = .0033). Increase of hemoglobin during treatment period showed a time profile favoring darbepoetin/iron with statistically significant effect from week 5 on. The safety profile was comparable in the two arms.In patients with chemotherapy-related anemia and no iron deficiency, IV iron supplementation significantly reduces treatment failures to darbepoetin without additional toxicity.
Vitamin D Receptor <i>Fok-I</i> Polymorphism Modulates Diabetic Host Response to Vitamin D Intake
Authors: Tirang R. Neyestani, Abolghassem Djazayery, Sakineh Shab-Bidar, Mohammad Reza Eshraghian, Ali Kalayi, Nastaran Shariátzadeh, Niloufar Khalaji, Malihe Zahedirad, A’zam Gharavi, Anahita Houshiarrad, Maryam Chamari, Sepideh Asadzadeh
Journal: Diabetes Care (2012)

Interpopulation as well as interindividual variations in response to vitamin D intake commonly observed in subjects with type 2 diabetes may be related to genetic makeup. One of the candidate genes potentially responsible for this diversity is vitamin D receptor (VDR). This study aimed to investigate the interactive effect of VDR Fok-I polymorphism and vitamin D intake on diverse aspects of diabetic host response.Glycemic status, lipid profiles, inflammatory biomarkers, and VDR Fok-I genotypes were determined in diabetic subjects (n = 140) who participated in a randomized controlled trial. Participants consumed two 250-mL bottles per day of yogurt drink (doogh) fortified with 500 IU vitamin D/250 mL for 12 weeks.Mean serum 25(OH)D increased by ~30 nmol/L (P < 0.001). The time × intervention effect was significant for 25(OH)D (P = 0.030), HDL (P = 0.011), high-sensitivity C-reactive protein (hsCRP) (P < 0.001), interleukin (IL)-4 (P = 0.008), and IL-6 (P = 0.017) among the genotypic groups. The alleles were defined as ''F'' or ''f'' depending on the absence or presence of the restriction site, respectively. The least increment in 25(OH)D was in ff (23.0 ± 3.8 nmol/L) compared with Ff (31.2 ± 3.4 nmol/L) and FF (35.6 ± 2.7 nmol/L) (P for trend = 0.009), but only the difference between ff and FF was significant (P = 0.023). FF group had the largest decrement of both hsCRP and IL-6 compared with Ff (P < 0.001 and P = 0.038) and ff (P = 0.010 and P = 0.048), respectively.We concluded that those of VDR ff genotype may be regarded as "low responders" to vitamin D intake in terms of response of circulating 25(OH)D and certain inflammatory biomarkers. A nutrigenetic approach may, therefore, be needed to protect diabetic patients from vitamin D deficiency.
THE “INDUCTION” OF DIHYDROFOLIC REDUCTASE ACTIVITY IN LEUKOCYTES AND ERYTHROCYTES OF PATIENTS TREATED WITH AMETHOPTERIN*
Authors: J. R. Bertino, D. M. Donohue, B. Simmons, B. W. Gabrio, R. Silber, F. M. Huennekens
Journal: Journal of Clinical Investigation (1963)

3) catalyzes the TPNH-dependent reduction of dihydrofolate to
Metabolic consequences of folate-induced reduction of hyperhomocysteinemia in uremia.
Authors: A F Perna, D Ingrosso, N G De Santo, P Galletti, M Brunone, V Zappia
Journal: Journal of the American Society of Nephrology (1997)

Plasma homocysteine, a well-recognized risk factor for cardiovascular disease, is elevated in uremic patients on hemodialysis. The authors have recently demonstrated that one consequence is the reduction in red cell membrane protein methylation levels, caused by a rise of intracellular adenosylhomocysteine, a potent inhibitor of methyltransferases. Protein methylation is involved in a repair mechanism of damaged membrane proteins, and an impairment in methylation leads to the accumulation of altered proteins. Therapy with folates, cofactors in the transformation of homocysteine to methionine, is effective in lowering plasma homocysteine. This article details a study on the metabolic effects of oral methyltetrahydrofolate, the active form of folic acid, on 14 uremic hemodialysis patients. Two months of therapy led to a significant reduction of plasma homocysteine levels, with a proportional response to pre-folate levels. In five of 13 patients with homocysteine levels above 20 microM, plasma homocysteine level was reduced to less than 15 microM. After treatment, levels of adenosylmethionine, the methyl donor in transmethylations, had significantly increased; levels of adenosylhomocysteine had increased to a smaller extent. Therefore, the ratio between the two compounds, an excellent indicator of the presence and the degree of methylation inhibition, was significantly ameliorated. Methionine plasma levels increased after treatment in all patients and were correlated with posttreatment adenosylmethionine levels. It was concluded that treatment with methyltetrahydrofolate brings the plasma homocysteine concentration back to an "acceptable" level, and the metabolic consequences are in the direction of an increase in the normal flow of transmethylations, as monitored by an increase in the [adenosylmethionine]/[adenosylhomocysteine] ratio.
Observations on Fifteen Cases of Haemoglobinuric Fever in British Central Africa
Authors: H. Hearsey
Journal: BMJ (1901)

THEMOGLOBINURIC FEVE;R may be defined as an disease, most probably of malarial origin, and by the occurrence of an extensive and rapid haemolysis. ETIOLOGY.Haemoglobinuric fever is endemic in British Central Africa, but nothing definite appears to be knowni as It occurs not only at the lake and river levels, the Shir6 highlands.There isno seasoni of the year during wlich it can be said to be most prevalent.This muclh certain: that it does not usually occur until after three years' residence in the country, is preceded attacks of malarial fever, and in the large quinine, antipyrin, or pheniacetiii have the patient during the febrile stage, and prior ment of haemoglobinuria.It would appear Conistitutions are more liable than others, and the fact that one attack predisposes to another.Indiains much less susceptible than Europeans to The period of incubation is unknown.SYxMPTO.IS AND COURSE.The prodromataconsist of a feeling of malaise, pains in limbs,lheadachle, discomfort in the nausea.
U.K. qualifying examination in dermatology
Authors: M.W. Greaves, F.A. Ive, M.M. Black, S. Bleehen, R. Camp, S. Comaish, A. Griffiths, K. Keczkes, D. McDonald, R. Marks, C.M. Ridley, A. Shrank, A. Warin, J. Wilkinson, C.F.H. Vickers, D. Burrows, R.A.J. Eady
Journal: British Journal of Dermatology (1984)

Journal Article U.K. qualifying examination in dermatology Get access M.W. Greaves, M.W. Greaves Search for other works by this author on: Oxford Academic Google Scholar F.A. Ive, F.A. Ive Search for other works by this author on: Oxford Academic Google Scholar M.M. Black, M.M. Black Search for other works by this author on: Oxford Academic Google Scholar S. Bleehen, S. Bleehen Search for other works by this author on: Oxford Academic Google Scholar R. Camp, R. Camp Search for other works by this author on: Oxford Academic Google Scholar S. Comaish, S. Comaish Search for other works by this author on: Oxford Academic Google Scholar A. Griffiths, A. Griffiths Search for other works by this author on: Oxford Academic Google Scholar K. Keczkes, K. Keczkes Search for other works by this author on: Oxford Academic Google Scholar D. McDonald, D. McDonald Search for other works by this author on: Oxford Academic Google Scholar R. Marks, R. Marks Search for other works by this author on: Oxford Academic Google Scholar ... Show more C.M. Ridley, C.M. Ridley Search for other works by this author on: Oxford Academic Google Scholar A. Shrank, A. Shrank Search for other works by this author on: Oxford Academic Google Scholar A. Warin, A. Warin Search for other works by this author on: Oxford Academic Google Scholar J. Wilkinson, J. Wilkinson Search for other works by this author on: Oxford Academic Google Scholar C.F.H. Vickers, C.F.H. Vickers Search for other works by this author on: Oxford Academic Google Scholar D. Burrows, D. Burrows Search for other works by this author on: Oxford Academic Google Scholar R.A.J. Eady R.A.J. Eady Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 110, Issue 1, 1 January 1984, Pages 121–122, https://doi.org/10.1111/j.1365-2133.1984.tb07322.x Published: 01 January 1984