tbuckley/cabot-search huggingface dataset:
Abstract A1: Clinical and biological significance of GSK-3β inactivation in breast cancer: An immunohistochemical study
Authors: Hanan Armanious, Jean Deschenes, Pascal Gelebart, Sunita Ghosh, John Mackey, Raymond Lai
Journal: Clinical Cancer Research (2010)

Abstract Glycogen synthase kinase 3β (GSK-3β), recently found to be functionally abnormal in various types of human disease, is negatively regulated by the PI3K/Akt signaling pathway. Since Akt is constitutively activated in a subset of breast cancer, we hypothesized that GSK-3β is inappropriately inactivated in these cases. In this study, we aimed to assess (1) the overall frequency of GSK-3β inactivation in breast cancer; (2) if there is an association between Akt activation and GSK-3β inactivation; and (3) whether there is correlation between GSK-3β inactivation and various pathologic and clinical parameters. The expression of the phosphorylated form of GSK-3β (pGSK-3β) and Akt (pAkt) were used as surrogate markers of GSK-3β inactivation and Akt activation, respectively. Immunohistochemistry applied to paraffin-embedded tissues was used to assess 72 consecutive invasive mammary carcinomas, of which 50 were estrogen receptor (ER)-positive. Overall, pGSK-3β and pAkt were positive in 34 (47.2%) and 35 (48.6%) cases, respectively. These two markers were significantly correlated with each other in the overall group and in the ER-positive subgroup (p=0.01 and 0.003, Spearman, respectively). Importantly, pGSK-3β, but not pAkt, significantly correlated a worse clinical outcome in this cohort (p=0.004, Log rank). In summary, evidence of GSK-3β inactivation was found in approximately half of the invasive mammary carcinomas. Our data suggest that this abnormality is likely attributed to Akt activation and that GSK-3β inactivation confers a worse clinical outcome. Citation Information: Clin Cancer Res 2010;16(14 Suppl):A1.
Reshuffling or inventing prosomeres: Expensive radiation or expensive neural tissue?
Authors: Andrei C. Miu, Adrian I. Olteanu
Journal: Behavioral and Brain Sciences (2003)

The target article is an elegant synthesis of the developmental and functional data and views on the evolutionary origin of the mammalian isocortex, integrating results from cell and molecular biology, experimental neuroanatomy, and chemoarchitectonic studies. Complementarily, we give here an account of two modes of isocortical evolution (prosomere reshuffling and invention) in terms of costs of radiation and neural tissue.
IL-1 has no direct role in the IGF-1 non-responsive state during experimentally induced arthritis in mouse knee joints.
Authors: P J Verschure, L A Joosten, F A Van de Loo, W B Van den Berg
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To investigate the involvement of interleukin-1 (IL-1) in the induction or maintenance of the insulin-like growth factor 1 (IGF-1) non-responsive state of chondrocytes during experimental arthritis in mouse knee joints. METHODS--To characterise IGF-1 nonresponsiveness during arthritis, we measured chondrocyte proteoglycan (PG) synthesis by assaying incorporation of 35S-sulphate into mouse patellar cartilage, obtained from knee joints with experimentally induced arthritis and normal knee joints, cultured with IGF-1. We investigated whether suppressive mediators produced by the arthritic synovium or chondrocytes abolished the IGF-1 stimulation of normal cartilage, and used IL-1 primed cartilage to mimic the arthritic in vivo state. Specific inflammatory mediators responsible for the maintenance of the suppressed IGF-1 response were sought. We measured IGF-1 responsiveness in normal and arthritic patellae cultured with antibodies against tumour necrosis factor (TNF) or IL-1 alpha/beta, with IL-1 receptor antagonist (IL-1ra), and with several inhibitors of proteolytic enzymes or reactive oxygen species, and analysed the role of IL-1 in the development of IGF-1 non-responsiveness by studying IGF-1 responses in cartilage treated with IL-1 antibodies in vivo, at the onset of arthritis. RESULTS--Mediators from the surrounding tissue of both normal and arthritic cartilage suppressed chondrocyte IGF-1 responses. Priming the cartilage with IL-1 did not directly induce IGF-1 non-responsiveness, but enhanced the ability of suppressive mediators from synovium or chondrocytes to downregulate the IGF-1 responsive state. IL-1ra, IL-1 alpha/beta antibody, TNF antibody, or the inhibitors tested did not markedly improve the disturbed IGF-1 response, but treatment with anti-IL-1 at the onset of arthritis prevented the development of IGF-1 non-responsiveness. CONCLUSION--IL-1 alone does not induce IGF-1 non-responsiveness and is not critical in the maintenance of this phenomenon. However, IL-1 does appear to be an important cofactor in the generation of the IGF-1 non-responsive state.
Limb Compression and Renal Impairment (Crush Syndrome) Complicating Narcotic Overdose
Authors: Saul N. Schreiber, Martin R. Liebowitz, Leslie H. Bernstein, K. Srinivasan
Journal: New England Journal of Medicine (1971)

WE have seen three drug addicts who had injected themselves with heroin 12 to 16 hours before admission and then lost consciousness, with one limb being compressed by another part of the body. The result was compression of the dependent limb and resultant "crush syndrome" with renal insufficiency.On admission the blood pressures averaged 100 systolic, 76 diastolic. The patients were dehydrated; the hematocrits were 55 to 58 per cent. The urines were dark, and the supernatants were benzidine positive. There were no red blood cells in the sediment. In one patient myoglobinuria was proved spectrophotometrically.Our first patient, in . . .
The role of active knee rom for posterior thigh muscle injuries prevention
Authors: A Siozos, N Malliaropoulos, D Tsiftsogloy, D Xristodoulou
Journal: British Journal of Sports Medicine (2011)

Athletes' physiological characteristics are fundamental both in terms of performance and injuries prevention. One of those is flexibility. Using an easy and cheap method, goniometry, estimating active knee range of motion (ROM) through the whole training and competing season, we can possibly lower the incidence of posterior thigh muscle injuries. Purpose The aim of our study was to assess the effects of repeated, on a regular basis, active knee ROM measurements in order to prevent posterior thigh muscles injuries (POTMI). Methods During 2006–2008 we followed up 100 Greek athletes (elite and non-elite) whose active knee ROM was measured in both sides. We estimated the active knee ROM related to their sport (runners-jumpers/sprinters-throwers), their performance (elite and non-elite ones) and their posterior thigh muscle injury rate. Results Jumpers/sprinters were found to have a statistically significant higher active knee ROM (&gt;71 ° ) in comparison with the runners (69.3 ° ) and throwers (69.4 ° ) group. Elite athletes' active knee ROM was higher than non-elite ones' and the difference reached statistical difference. Finally elite athletes were found to have fewer and less severe injuries than the non-elite ones. Conclusion Our results suggest that Jumpers/sprinters have generally higher active knee ROM than other track and field athletes. Elite athletes were found to have higher active knee ROM than non-elite ones. That seems to protect them from injuries of the hamstring muscles. Active knee ROM measurement can be an easy and practical method of follow-up and a useful tool for injury prevention.
In vitro generation of human cytomegalovirus pp65 antigenemia, viremia, and leukoDNAemia.
Authors: M G Revello, E Percivalle, E Arbustini, R Pardi, S Sozzani, G Gerna
Journal: Journal of Clinical Investigation (1998)

Immunocompromised patients with disseminated human cytomegalovirus (HCMV) infection have circulating PMN carrying HCMV pp65 (antigenemia), infectious virus (viremia), and viral DNA (leukoDNAemia). Because HCMV does not fully replicate in PMN, it is generally hypothesized that virions and viral materials are taken up by phagocytosis from fully permissive HCMV-infected endothelial cells. However, no experimental evidence has ever been provided for these PMN-endothelium interactions. PMN from 11 donors were cocultured with endothelial cells infected with an endothelium-adapted HCMV strain and with human fibroblasts infected with low-passaged clinical and laboratory-adapted HCMV strains. pp65-positive PMN were detected after coculture with both HCMV-infected endothelial and fibroblast cells, provided that wild and not laboratory-adapted strains were used. In addition, cocultured PMN carried infectious virus as demonstrated by virus isolation and presence of complete virus particles by electron microscopy. Moreover, high levels of viral DNA were consistently detected by quantitative PCR in cocultured PMN. Thus, we have generated in vitro the three most important viral parameters detected in patients with disseminated HCMV infection (antigenemia, viremia, and leukoDNAemia). The failure of laboratory-adapted HCMV strain to induce this phenomenon demonstrates that important modifications have occurred in attenuated viral strains affecting basic biological functions.
Marked elevation of myocardial trace elements in idiopathic dilated cardiomyopathy compared with secondary cardiac dysfunction
Authors: Andrea Frustaci, Nicola Magnavita, Cristina Chimenti, Marina Caldarulo, Enrico Sabbioni, Romano Pietra, Carlo Cellini, Gian Federico Possati, Attilio Maseri
Journal: Journal of the American College of Cardiology (1999)
Abstract 1661: Autophagy induced by cathepsin S inhibition causes early ROS production for oxidative DNA damage and subsequent cell death.
Authors: Chien-Chang Huang, Jang-Yang Chang
Journal: Cancer Research (2013)

Abstract Cathepsin S plays multiple roles in MHC class II antigen presentation, extracellular matrix degradation, angiogenesis, and tumorogenesis. Pharmacological inhibition of cathepsin S activity not only inhibits tumor invasion and angiogenesis but also reduces cell viability. Herein, we investigate the molecular executioner which responsible for targeting cathepsin S-induced cell death and its association with autophagy. Surprisingly, distinct from the classical regulation of autophagy by ROS, autophagy, rather than mitochondrial process, is the genuine regulator of early ROS production which responsible for consequent oxidative DNA damage and cell death. Molecular silencing of autophagy-dependent ATG genes and pharmacologic inhibition of autophagy with 3-MA and wortmannin significantly reduced ROS production, oxidative DNA damage, and cell death. Collectively, this study reveals a non-canonical molecular pathway where after the inhibition of cathepsin S, autophagy up-regulates ROS production for oxidative DNA damage and subsequently contributes to autophagy-dependent cell death. (This work was supported by the following grants: Department of Health, Taiwan DOH99-TD-C-111-004, National Health Research Institutes CA-101-PP-22, and National Research Program for Biopharmaceuticals 100CAP015-5) Citation Format: Chien-Chang Huang, Jang-Yang Chang. Autophagy induced by cathepsin S inhibition causes early ROS production for oxidative DNA damage and subsequent cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1661. doi:10.1158/1538-7445.AM2013-1661
The Role of Gefitinib Treatment for Korean Never-Smokers with Advanced or Metastatic Adenocarcinoma of the Lung: A Prospective Study
Authors: Dae Ho Lee, Ji-Youn Han, Sun Young Yu, Hyae Young Kim, Byung-Ho Nam, Eun Kyung Hong, Heung Tae Kim, Jin Soo Lee
Journal: Journal of Thoracic Oncology (2006)
Ground Squirrel Hepatitis Virus Infection
Authors: Patricia L. Marion, Susan S. Knight, Felix H. Salazar, Hans Popper, William S. Robinson
Journal: Hepatology (2007)

Twenty-four adult Beechey ground squirrels persistently infected with the hepatitis B virus-related ground squirrel hepatitis virus (GSHV) remained infected with high levels of viral surface antigen (GSHsAg) and virion-associated DNA polymerase activity in the blood for over 2 years in captivity. Unlike humans infected with hepatitis B virus, no GSHsAg-bearing ground squirrels had surface antigen in the blood without DNA polymerase-containing virions, and the levels of these did not change. Only a very mild hepatitis was observed histologically in some of the virus-infected animals, with faint Shikata-staining detectable in some. Other animals exhibited no histologic evidence of hepatitis. While the closely related woodchuck hepatitis virus has been associated with more severe chronic hepatitis and a high incidence of liver cancer in woodchucks, these were not found in GSHV-infected ground squirrels when a similar number of animals were followed for a similar time of observation. Experimental infection of ground squirrels with no evidence of current or past GSHV infection resulted in three types of response: (i) self-limited or transient GSHV-positive infection; (ii) GSHV-positive infection which became persistent, and (iii) primary anti-GSHs and anti-GSHc (antibody to the viral core antigen) responses without detectable GSHsAg or virion DNA polymerase activity in the blood. These responses are similar to those observed following experimental infection of man with HBV. GSHV produced none of the three responses when injected into a variety of laboratory animal species and a chimpanzee, causing only an antibody response to GSHsAg. No evidence of current or past infection was detected in a number of animal species from an area endemic for GSHV. The virus has only been found in one area of northern California, with a carrier rate in that location reaching 52%.
S131 Fatigue in bronchiectasis: its relationship to pseudomonas colonisation, dyspnoea and airflow obstruction
Authors: J. G. Macfarlane, H. Tedd, P. McAlinden, T. Small, L. Rostron, J. Newton, A. De Soyza
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Fatigue is a complex and disabling symptom in non-CF bronchiectasis (nCF-Br) and can be formally measured using the Fatigue Impact Scale (FIS). FIS scores of &gt;40 out of 120 are clinically significant. The FIS score has been shown to be prognostic of premature death in Primary Biliary cirrhosis but is not linked to markers of organ dysfunction (liver function tests). As poorer outcomes have been recently reported in <i>Pseudomonas</i> infected nCF-Br patients we aimed to measure the correlation between FIS scores and parameters of severity in nCF-Br, for example, <i>Pseudomonas</i> infection, degree of dyspnoea and airflow obstruction. <h3>Methods</h3> FEV<sub>1</sub>% predicted, MMRC dyspnoea score (MMRCD) and FIS were recorded in stable adult nCF-Br patients attending specialist clinic. All previous sputum cultures isolating <i>Pseudomonas aeruginosa</i> were reviewed. Two groups of patients were studied: those with <i>Pseudomonas</i> ‘colonisation’ (organism cultured ≥2 occasions, 3 months apart within 1-year period) and those with ‘isolation’ (organism cultured ≥1 occasion). Statistical comparison used χ<sup>2</sup>, Fisher9s correlation and Mann–Whitney U tests. <h3>Results</h3> 73F, 41M patients were included; average age 60 (range 24–90) with an average FEV<sub>1</sub> 66% predicted (SD +/−26%). 54 (47%) patients had <i>Pseudomonas</i> isolation; 38 (33%) patients had colonisation. Fatigue levels were similar in patients with and without colonisation (median 48.5 vs 36.5, p=0.31). Significant fatigue (FIS&gt;40) was more common in patients with <i>Pseudomonas</i> isolation (47%) than those with no previous isolates (p=0.04, OR=2.2) However, fatigue levels, although increased, were not significantly different (median FIS 50 vs 32; p=0.064). Fatigue correlated with MMRCD (r=0.54, p&lt;0.0001) but less well with FEV<sub>1</sub>% predicted (r=0.2, p=0.04). FEV<sub>1</sub>% predicted was lower in patients with <i>Pseudomonas</i> colonisation (median FEV<sub>1</sub> 49% vs 74%, p=0.0007) and in patients with <i>Pseudomonas</i> isolation (median FEV<sub>1</sub> 52% vs 74%, p=0.002). <h3>Conclusions</h3> <i>Pseudomonas</i> infection (past or present) appears to be associated with greater clinically significant fatigue scores and poorer lung function. Fatigue doesn9t strongly correlate with FEV<sub>1</sub> % predicted but is correlated with MMRCD. Further regression analysis of variables is underway to understand these inter relationships further. Systemic aspects of Pseudomonas infection may be different to other infections explaining the divergence.
Mobility after amputation of a lower limb
Authors: J R Kulkarni
Journal: BMJ (1995)

Self evaluation and group evaluation also play an important part in the efficient running of a problem based learning group: they allow students to identify their own strengths and weaknesses and thus help to modify individual and group learning processes.Tutors' effectiveness is also scrutinised.Evaluation not only helps to improve individual and group function but also identifies those students who are having difficulties, so that re- medial strategies can be started.Students do learn effectively in a problem based learning system.They learn not only about the basic science of a problem but also about the many ethical considerations of modern medicine and the impact of disease on the family and community.It is thrilling to work with a group of students who enjoy learning medicine: the tutor learns a lot too.
Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity
Authors: Collin J Kreple, Yuan Lu, Rebecca J Taugher, Andrea L Schwager-Gutman, Jianyang Du, Madeliene Stump, Yimo Wang, Ali Ghobbeh, Rong Fan, Caitlin V Cosme, Levi P Sowers, Michael J Welsh, Jason J Radley, Ryan T LaLumiere, John A Wemmie
Journal: Nature Neuroscience (2014)
Serum immunoreactive gastrin in rheumatoid arthritis. Further observations on its identity, clinical specificity, and relationship to gastric function.
Authors: P J Rooney, A C Kennedy, G H Gray, R D Sturrock, K D Buchanan, W C Dick
Journal: Annals of the Rheumatic Diseases (1976)

Serum immunoreactive gastrin is raised in some patients with rheumatoid arthritis (RA). In this paper paired samples taken within 30 minutes of each other show that this phenomenon is reproducible. Dilution curves show identity between gastrin from RA patients and from patients with no RA, and the raised immunoreactive gastrin concentration is demonstrable in patients who do not have chronic atrophic gastritis and in whom both basal and stimulated acid output concentrations are normal. Samples of gastric mucous membrane obtained from the body of the stomach and gastroscopy under direct vision in 18 patients with raised serum immunoreactive gastrin concentrations were normal.
Cutaneous Nodule in a Young Man
Authors: Jianjun Qiao, Hong Fang
Journal: JAMA (2012)

A 21-YEAR-OLD MALE STUDENT PRESENTS WITH A NODULE ON HIS CHEST THAT has been progressively enlarging over 1 month. He also has a 1-month history of upper abdominal pain associated with diarrhea but without fever or chills. He was diagnosed with acute gastroenteritis and treated with oral omeprazole and ofloxacin without relief. He has lost 5 kg during the past half year. He denies any history of chronic illness or family history of cancer. Physical examination reveals left supraclavicular and cervical lymphadenopathy. A solitary asymptomatic, nontender, and indurated nodule is found on his chest (FIGURE 1). Gastrointestinal endoscopy shows multiple ulcers on the gastric fundus and gastric corpus. What Would You Do Next?
Profibrinolytic, Antithrombotic, and Antiinflammatory Effects of an Insulin-Sensitizing Strategy in Patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial
Authors: Burton E. Sobel, Regina M. Hardison, Saul Genuth, Maria M. Brooks, Robert D. McBane, David J. Schneider, Richard E. Pratley, Kurt Huber, Robert Wolk, Ashok Krishnaswami, Robert L. Frye
Journal: Circulation (2011)

Background— Effects were compared in patients in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial of 2 mechanistically different strategies for treatment of hyperglycemia, insulin-sensitizing and insulin-providing strategies, on biomarker profiles reflecting the balance between fibrinolysis and thrombosis and the intensity of inflammation implicated in diabetic vasculopathy. Methods and Results— A total of 2368 patients with type 2 diabetes mellitus and clinically stable, angiographically documented coronary artery disease were randomized to treatment with 1 of the 2 strategies and followed for an average of 5 years. Plasminogen activator inhibitor type 1 antigen and activity, tissue plasminogen activator antigen, fibrinogen, D-dimer, C-reactive protein, insulin, and hemoglobin A 1c were assayed in blood samples acquired at baseline and at 12 regular intervals throughout the follow-up interval. Higher baseline D-dimer, fibrinogen, and C-reactive protein portended a poor prognosis in patients in both groups. In contrast to the insulin-providing strategy, the insulin-sensitizing strategy led to (1) lower plasma insulin; (2) lower plasminogen activator inhibitor type 1 antigen and activity and lower tissue plasminogen activator antigen (known to track with plasminogen activator inhibitor type 1); and (3) lower C-reactive protein and fibrinogen at all intervals after baseline ( P &lt;0.001 for each). Conclusions— The insulin-sensitizing treatment strategy led to changes in biomarker profiles indicative of decreased insulin resistance, an altered balance between thrombosis and fibrinolysis favoring fibrinolysis, and diminished intensity of the systemic inflammatory state, factors that have been associated with cardiovascular risk. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00006305.
Reproducibility of Standardized Bronchial Allergen Provocation Test
Authors: L. Frølund, F. Madsen, U. Gerner Svendsen, B. Weeke
Journal: Allergy (1986)

Standardized bronchial allergen provocation was performed twice (with an interval of median 14 days (range 14-44)) in 19 extrinsic, well-defined asthmatic patients to study the reproducibility of the bronchial response. Smoking and medications were strictly withheld prior to the provocation. Ten-fold increasing concentrations of allergen solution 0.9 ml were inhaled by tidal volume breathing for 5 min at 10-min intervals. The actual dose given was expressed by the concentration of the solution used. Forced expiratory volume in the first second (FEV1) was used to determine responses, and the provocation continued until an allergen concentration (allergen PC20) was reached which caused at least 20% decrease of the post-saline FEV1. All provocations were followed by a bronchial reaction within clinically acceptable limits. The reproducibility was high, evaluated by the Spearman rank correlation coefficient Rho = 0.90 (P less than 0.01). It is concluded that bronchial provocation with allergens performed as outlined in this study represents a reproducible test which can be applied in routine allergy diagnostics, and in further investigations concerning specific bronchial reactivity.