tbuckley/cabot-search huggingface dataset:
Transcriptional Activation of p21waf1/cip1 by Alkylphospholipids
Authors: Adriana De Siervi, Maria Marinissen, Jessica Diggs, Xiao-Fan Wang, Gilles Pages, Adrian Senderowicz
Journal: Cancer Research (2004)

Abstract Alkylphospholipids (ALKs) are a novel class of antitumor agents with an unknown mechanism of action. The first ALK tested in the clinic, miltefosine, has been approved recently in Europe for the local treatment of patients with cutaneous metastasis. Perifosine, the only available oral ALK, is being studied currently in human cancer clinical trials. We have shown previously that perifosine induces p21waf1/cip1 in a p53-independent fashion and that induction of p21waf1/cip1 is required for the perifosine-induced cell cycle arrest because cell lines lacking p21waf1/cip1 are refractory to perifosine. In this report, we investigated the mechanism by which perifosine induces p21waf1/cip1 protein expression. We observed that perifosine induces the accumulation of p21waf1/cip1 mRNA without affecting p21waf1/cip1 mRNA stability. Using several p21waf1/cip1 promoter-driven luciferase reporter plasmids, we observed that perifosine activates the 2.4-kb full-length p21waf1/cip1 promoter as well as a p21 promoter construct lacking p53-binding sites, suggesting that perifosine activates the p21waf1/cip1 promoter independent of p53. The minimal p21 promoter region required for perifosine-induced p21 promoter activation contains four consensus Sp1-binding sites. Mutations in each particular Sp1 site block perifosine-induced p21waf1/cip1 expression. Moreover, we showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of Sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased Sp1 binding and enhanced p21waf1/cip1 transcription. These results represent a novel mechanism by which alkylphospholipids modulate transcription, and may contribute to the discovery of new signal transduction pathways crucial for normal and neoplastic cell cycle control.
Intensified alemtuzumab–CHOP therapy for peripheral T-cell lymphoma
Authors: H.C. Kluin-Nelemans, M. van Marwijk Kooy, P.J. Lugtenburg, W.L.J. van Putten, M. Luten, J. Oudejans, G.W. van Imhoff
Journal: Annals of Oncology (2011)
Shockwave treatment for medial tibial stress syndrome in athletes; a prospective controlled study
Authors: M H Moen, S Rayer, M Schipper, S Schmikli, A Weir, J L Tol, F J G Backx
Journal: British Journal of Sports Medicine (2011)

Objective The purpose of this study was to describe the results of two treatment regimens for medial tibial stress syndrome (MTSS); a graded running programme and the same running programme with additional shockwave therapy (extracorporeal shockwave therapy; ESWT). Design A prospective observational controlled trial. Setting Two different sports medicine departments. Participants 42 athletes with MTSS were included. Intervention Patients from one hospital were treated with a graded running programme, while patients from the other hospital were treated with the same graded running programme and focused ESWT (five sessions in 9 weeks). Main Outcome Measures Time to full recovery (the endpoint was being able to run 18 min consecutively without pain at a fixed intensity). Results The time to full recovery was significantly faster in the ESWT group compared with the patients who only performed a graded running programme, respectively 59.7±25.8 and 91.6±43.0 days (p=0.008). Conclusions This prospective observational study showed that MTSS patients may benefit from ESWT in addition to a graded running programme. ESWT as an additional treatment warrants further investigation in a prospective controlled trial with the addition of randomisation and double blinding.
A mathematical model of the dynamic geometry of the intact left ventricle and its application to clinical data.
Authors: J G Dumesnil, R M Shoucri, J L Laurenceau, J Turcot
Journal: Circulation (1979)

In this paper we examine the relations that may exist between the geometric variables most frequently used to describe left ventricular contraction. The left ventricle is represented by a thick-walled cylinder contracting both radially and longitudinally. For this model, wall thickening, mid-wall radius shortening and longitudinal axis shorteining can be shown to be uniquely related during contraction, whereas it can be demonstrated that internal radius shortening is not uniquely related to these variables, but is also determined by the specific geometry of the cylinder, expressed in terms of the mid-wall radius-to-wall thickness (R/h) ratio of the cylinder. Detailed analysis of the same variables in 44 normal subjects, 32 patients with aortic stenosis and 54 patients with valvular regurgitation (33 aortic and 21 mitral), strongly suggests that the same relations are also clinically applicable. For instance, ventricular longitudinal axis shortening can be estimated with some accuracy from the standard M-mode echocardiogram. Also, wall thickening can be viewed as the direct reflection of the shortening that occurs in the circumferential and longitudinal directions, whereas internal radius shortening is significantly influenced by the R/h ratio of the ventricle, a consideration which becomes important when analyzing results in patients with left ventricular hypertrophy.
Mineral Metabolites and CKD Progression in African Americans
Authors: Julia J. Scialla, Brad C. Astor, Tamara Isakova, Huiliang Xie, Lawrence J. Appel, Myles Wolf
Journal: Journal of the American Society of Nephrology (2012)

CKD progresses more rapidly to ESRD among African Americans compared with Caucasians. Disordered mineral metabolism is more severe among African Americans with CKD, which might partially explain the accelerated progression of their kidney disease. Here, using data from the African American Study of Kidney Disease and Hypertension, we evaluated longitudinal changes in serum levels of fibroblast growth factor-23 (FGF23), parathyroid hormone (PTH), phosphate, and 25-hydroxyvitamin D in a subset of 420 participants followed for a median of 4 years. We also examined the association of baseline levels of mineral metabolites with risk for ESRD or death in 809 participants. FGF23, PTH, and phosphate levels rose over time; participants with faster rates of decline in measured GFR had the greatest increases in these parameters (P<0.01 for each). Higher baseline levels of FGF23, PTH, and phosphate each associated with increased risk for ESRD or death independent of GFR. FGF23 exhibited a dose-response relationship with outcomes (HR=1.30 per doubling, 95% CI=1.15-1.47; HR=2.24 for highest compared with lowest quartile, 95% CI=1.39-3.60), whereas PTH and phosphate showed nonlinear relationships. Vitamin D insufficiency (<30 ng/ml) was present in 95% of participants, but lower levels did not independently associate with outcomes. Using death-censored ESRD as the outcome produced qualitatively similar results. In conclusion, abnormalities of mineral metabolism worsen with progressive CKD and associate with higher risk for ESRD among African Americans with hypertensive nephrosclerosis.
Alpha Antitrypsin Deficiency and Pulmonary Emphysema
Authors: C A Guenter, M H Welch, J F Hammarsten
Journal: Annual Review of Medicine (1971)

The association of familial alphat antitrypsin deficiency and pulmonary emphysema was first recognized by Laurell & Eriksson ( 1). This observa­ tion was particularly significant because it identified an important relation­ ship between a biochemical abnormality and a common but poorly under­ stood type of lung injury, a relationship that may represent the first docu­ mented disease resulting from a deficiency of proteinase inhibitors. In this review we have summarized the available information regarding the char­ acteristics of serum proteinase inhibitors, the incidence and type of pulmo­ nary disease associated with familial alphal antitrypsin deficiency, and the evidence that pulmonary tissue injury may be related to the deficiency of these inhibitors.
Measurement of shoulder related disability: results of a validation study.
Authors: P Croft, D Pope, M Zonca, T O'Neill, A Silman
Journal: Annals of the Rheumatic Diseases (1994)

To develop and validate a questionnaire to quantify disability associated with shoulder symptoms.A set of questions relevant to shoulder symptoms from a general disability interview was developed and the questionnaire applied to a cross-sectional population survey and a prospective study of general practice attenders. Subjects included adults who reported current shoulder pain in a population survey and patients from three general practices who attended with shoulder symptoms during a six month period. The main outcome measures were: frequency of problems with daily living related to shoulder symptoms, total score on 22-item disability questionnaire, and measures of shoulder movement.A higher proportion (80%) of patients attending their general practitioner with shoulder symptoms had five or more disabilities compared with subjects reporting shoulder pain in a community survey (34%). The ranked frequency with which each disability was reported was similar in the two groups, although sleep disturbance was the most common problem in consulters. Self-reported disability is correlated with measures of restricted shoulder movement.This disability questionnaire was simple to complete and should prove useful for both general practice and population-based studies of shoulder pain.
Chimerism after Liver Transplantation for Type IV Glycogen Storage Disease and Type 1 Gaucher's Disease
Authors: Thomas E. Starzl, Anthony J. Demetris, Massimo Trucco, Camillo Ricordi, Suzanne Ildstad, Paul I. Terasaki, Noriko Murase, Ross S. Kendall, Mirjana Kocova, William A. Rudert, Adriana Zeevi, David Van Thiel
Journal: New England Journal of Medicine (1993)

Liver transplantation for type IV glycogen storage disease (branching-enzyme deficiency) results in the resorption of extrahepatic deposits of amylopectin, but the mechanism of resorption is not known.
Psychopathologic and Metabolic Changes in a Patient with Myxedema Psychosis Treated with L-tri-iodothyronine
Authors: MYRON L. GLUCKSMAN, E. STOKES
Journal: American Journal of Psychiatry (1967)

L-tri-iodothyronine was utilized in the treatment of myxedema psychosis. Psychopathology and metabolic state were carefully documented throughout the course of treatment. Part of the psychopathology observed was an organic brain syndrome related to the myxedema. Treatment with L-tri-iodothyronine resulted in disappearance of the organic brain syndrome and return to the euthyroid state. Persisting psychopathology appears related either to a premyxedematous depressive illness or to the response of the patient's personality to the myxedematous state. This segment of the psychopathology was responsive to chlorpromazine and electroconvulsive treatments.
Contribution of multiple inert gas elimination technique to pulmonary medicine. 1. Principles and information content of the multiple inert gas elimination technique.
Authors: J Roca, P D Wagner
Journal: Thorax (1994)

This introductory review summarises four different aspects of the multiple inert gas elimination technique (MIGET). Firstly, the historical background that facilitated, in the mid 1970s, the development of the MIGET as a tool to obtain more information about the entire spectrum of VA/Q distribution in the lung by measuring the exchange of six gases of different solubility in trace concentrations. Its principle is based on the observation that the retention (or excretion) of any gas is dependent on the solubility (lambda) of that gas and the VA/Q distribution. A second major aspect is the analysis of the information content and limitations of the technique. During the last 15 years a substantial amount of clinical research using the MIGET has been generated by several groups around the world. The technique has been shown to be adequate in understanding the mechanisms of hypoxaemia in different forms of pulmonary disease and the effects of therapeutic interventions, but also in separately determining the quantitative role of each extrapulmonary factor on systemic arterial PO2 when they change between two conditions of MIGET measurement. This information will be extensively reviewed in the forthcoming articles of this series. Next, the different modalities of the MIGET, practical considerations involved in the measurements and the guidelines for quality control have been indicated. Finally, a section has been devoted to the analysis of available data in healthy subjects under different conditions. The lack of systematic information on the VA/Q distributions of older healthy subjects is emphasised, since it will be required to fully understand the changes brought about by diseases that affect the older population.
Effect of Respiratory Alkalosis on Survival in Hemorrhagic Shock
Authors: MARTIN BRANDFONBRENER, ROBERT WHANG
Journal: Circulation Research (1967)

The effect of respiratory alkalosis on survival in hemorrhagic shock was studied in pentobarbital-anesthetized dogs. Since cell membranes are relatively poorly permeable to bicarbonate ion, production of alkalosis by hyperventilation may influence intracellular pH more than by bicarbonate infusion. Hyperventilation was produced by increasing tidal volume in one group of dogs. Spontaneously breathing dogs served as controls. Another control group in which ventilation was maintained with a respirator to produce normal blood gas values was also studied. Shock was produced by arterial bleeding at a fixed rate to maintain blood pressure at 50 mm Hg for 90 min, then at 30 mm Hg for 45 min. The blood was then reinfused. In the hyperventilation group 7 of 9 animals survived 480 min with a blood pressure greater than 75 mm Hg, while none of 8 in the control group and none of 7 in which ventilation was maintained at the normal level survived with these criteria. Arterial pH was higher in the hyperventilation than the other groups, while differences in Pao 2 were not significant throughout most of the experiment. Hyperventilation improved survival and hemorrhagic shock, probably related to the changes in pH.
Closed Relation Between Carotid and Ascending Aortic Atherosclerosis in Cardiac Patients
Authors: I. E. Kallikazaros, C. P. Tsioufis, C. I. Stefanadis, C. E. Pitsavos, P. K. Toutouzas
Journal: Circulation (2000)

Carotid atherosclerosis and aortic atherosclerosis are both associated with coronary artery disease and cerebral thromboembolism. However, the relationship between asymptomatic carotid and aortic atherosclerosis is not well known.Sixty-two consecutive cardiac patients (mean age 57 years) without a history of atherosclerotic cardiovascular disease who were referred for transesophageal echocardiography were included. By means of a high-resolution ultrasound technique, normal carotid arteries were found in 12 patients (19.4%), whereas 15 patients (24. 2%) had increased intima-media thickness, and the remaining 35 patients (56.5%) had atherosclerotic plaques (intima-media thickness >/=1.3 mm). Transesophageal echocardiography characterized ascending aortic intimal morphology as normal in 1 patient (1.6%), as thickening in 22 patients (35.5%), and as atherosclerotic plaques in 39 patients (62.9%). Patients with both carotid and aortic plaques were older compared with patients without plaques; also, a higher percentage of patients with carotid and aortic plaques suffered from hypertension and diabetes mellitus compared with patients without plaques (P:<0.001). The incidence of carotid plaques was 74.3% (29 of 39 patients) in the subgroup with aortic plaques; there was a stepwise increase in the percentage of patients with carotid plaques among the patients with increasing grades of aortic atherosclerosis. Furthermore, the incidence of ascending aortic plaques was 82.8% (29 of 35 patients) in the subgroup with carotid plaques. Regression analysis revealed that age and carotid plaques were independently related to the presence of aortic plaques. In the entire study population, the presence of carotid plaques had a high positive predictive value (83%), an acceptable sensitivity (75%) and specificity (74%), and a relatively low negative predictive value (63%) for the presence of aortic plaques.In cardiac patients without clinical evidence of atherosclerotic cardiovascular disease, a high prevalence of combined aortic and carotid plaques were detected. The presence of carotid plaque reflects the presence of aortic plaque, whereas the absence of carotid plaque may not reflect the absence of aortic plaque.
Dose Effect of Clopidogrel Reloading in Patients Already on 75-mg Maintenance Dose
Authors: Jean-Philippe Collet, Johanne Silvain, Antoine Landivier, Marie-Laure Tanguy, Guillaume Cayla, Anne Bellemain, Nicolas Vignolles, Sophie Gallier, Farzin Beygui, Ana Pena, Gilles Montalescot
Journal: Circulation (2008)

Clopidogrel loading has mostly been studied in clopidogrel-naïve patients. Whether clopidogrel-treated patients readmitted for an acute coronary syndrome or percutaneous coronary intervention can benefit from a new load of clopidogrel and at what dose remain unknown. Our aim was to evaluate the impact of 3 different strategies of administration of a loading dose of 900 mg clopidogrel in patients already treated with a maintenance dose of 75 mg clopidogrel for at least 7 days on residual platelet aggregation.Patients treated long term by clopidogrel 75 mg/d were assigned to receive a first loading dose of 300, 600, or 900 mg clopidogrel and 4 hours later a second loading dose of 600, 300, or 0 mg, respectively, to achieve a total loading dose of 900 mg in all patients. Platelet aggregation was evaluated at baseline, at 4 hours after the initial load (and before second load), and at 24 hours using light transmission aggregometry with 20 micromol ADP and the point-of-care assay VerifyNow P2Y(12). The primary objective of the study was to evaluate the inhibition (relative change) of residual platelet aggregation (percentage of IRPA) between 600- and 900-mg first loading at 4 hours. IRPA at 24 hours also was evaluated as a secondary objective, as well as the rate of suboptimal response at 4 hours defined as IRPA <10%. We included 166 consecutive patients with acute coronary syndromes (n=80, 48%) or stable coronary artery disease (n=86, 52%). Baseline characteristics were similar in the 3 dose groups. A significant stepwise increase was found in percentage IRPA assessed at 4 hours in patients initially assigned to 300 versus 600 versus 900 mg (30.7% versus 40.3% versus 64.0%, respectively; P=0.0024). The difference in percentage IRPA at 4 hours was not significant between 300 and 600 mg but was significant between 600 and 900 mg and between 300 and 900 mg. Percentage IRPA assessed at 24 hours when all patients had received 900 mg did not differ between the 3 loading regimens. The rates of suboptimal response (IRPA <10% at 4 hours) were 23.6%, 20.4%, and 5.3% with 300, 600, and 900 mg, respectively (P=0.02 for all).In patients treated long term with 75 mg clopidogrel, a new loading dose of 900 mg improves IRPA and reduces poor and/or slow response to clopidogrel significantly more than that obtained with 300 or 600 mg.
Low-dose low-molecular-weight heparin (enoxaparin) is beneficial in lichen planus: a preliminary report
Authors: Emmilia Hodak, Gil Yosipovitch, Michael David, Arieh Ingber, Liran Chorev, Ofer Lider, Leora Cahalon, Irun R. Cohen
Journal: Journal of the American Academy of Dermatology (1998)
Cost-effectiveness of one versus two sample faecal immunochemical testing for colorectal cancer screening
Authors: S Lucas Goede, Aafke H C van Roon, Jacqueline C I Y Reijerink, Anneke J van Vuuren, Iris Lansdorp-Vogelaar, J Dik F Habbema, Ernst J Kuipers, Monique E van Leerdam, Marjolein van Ballegooijen
Journal: Gut (2012)

The sensitivity and specificity of a single faecal immunochemical test (FIT) are limited. The performance of FIT screening can be improved by increasing the screening frequency or by providing more than one sample in each screening round. This study aimed to evaluate if two-sample FIT screening is cost-effective compared with one-sample FIT.The MISCAN-colon microsimulation model was used to estimate costs and benefits of strategies with either one or two-sample FIT screening. The FIT cut-off level varied between 50 and 200 ng haemoglobin/ml, and the screening schedule was varied with respect to age range and interval. In addition, different definitions for positivity of the two-sample FIT were considered: at least one positive sample, two positive samples, or the mean of both samples being positive.Within an exemplary screening strategy, biennial FIT from the age of 55-75 years, one-sample FIT provided 76.0-97.0 life-years gained (LYG) per 1000 individuals, at a cost of € 259,000-264,000 (range reflects different FIT cut-off levels). Two-sample FIT screening with at least one sample being positive provided 7.3-12.4 additional LYG compared with one-sample FIT at an extra cost of € 50,000-59,000. However, when all screening intervals and age ranges were considered, intensifying screening with one-sample FIT provided equal or more LYG at lower costs compared with two-sample FIT.If attendance to screening does not differ between strategies it is recommended to increase the number of screening rounds with one-sample FIT screening, before considering increasing the number of FIT samples provided per screening round.
NSAIDs for the Chemoprevention of Oral Cancer: Promise or Pessimism?
Authors: Susan Goodin, Steven J. Shiff
Journal: Clinical Cancer Research (2004)

Oral cancer causes considerable morbidity and is associated with a 5-year survival rate of less than 50%. It is a major problem in populations in which alcohol and tobacco use are prevalent such as in lower socioeconomic communities. Oral cancer, like cancers in many other sites, is often preceded
New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes
Authors: Raffaele De Caterina, Steen Husted, Lars Wallentin, Raffaele De Caterina, Steen Husted, Lars Wallentin, Felicita Andreotti, Harald Arnesen, Fedor Bachmann, Colin Baigent, Kurt Huber, Jørgen Jespersen, Steen Dalby Kristensen, Gregory Y.H. Lip, João Morais, Lars Hvilsted Rasmussen, Agneta Siegbahn, Freek W.A. Verheugt, Jeffrey I. Weitz
Journal: Journal of the American College of Cardiology (2012)
Low Dose <i>Leishmania major</i> Promotes a Transient T Helper Cell Type 2 Response That Is Down-regulated by Interferon γ–producing CD8+ T Cells
Authors: Jude E. Uzonna, Karen L. Joyce, Phillip Scott
Journal: The Journal of Experimental Medicine (2004)

An unresolved issue in the field of T helper (Th) cell development relates to the findings that low doses of antigen promote Th2 cell development in vitro, whereas several classic in vivo studies suggest the opposite. Here we resolve this paradox by studying the early immune response in mice after infection with different doses of Leishmania major. We found that low parasite doses induced a Th2 response in C57BL/6 (B6) mice, whereas high doses induced a Th1 response. However, the Th2 response in low dose–infected mice was transient and the animals healed. The appearance of a Th1 response after low dose infection was dependent upon the concomitant activation of interferon γ–producing CD8+ T cells. In the absence of CD8+ T cells, the Th2 response was maintained. However, either neutralization of interleukin (IL)-4 or administration of IL-12 promoted a Th1 response after low dose infection of CD8-deficient mice, indicating that the required role for CD8+ T cells was limited to modulation of CD4+ T cell responses. Thus, the discrepant results seen between in vivo and in vitro studies on the effects of antigen dose on Th cell differentiation may depend upon whether CD8+ T cells participate in the immune response.