tbuckley/cabot-search huggingface dataset:
Changes of igg-bearing cell populations in the portal tracts of patients with chronic liver disease of viral etiology: An evaluation by immunoperoxidase method and computerized image analysis
Authors: Giuseppe Torgano, Maurizio Vecchi, Eliana Arosio, Daniela Santambrogio, Guido Ronchi, Giorgio Annoni, Maurizio Tomasini, Ettore Contessini, Roberto De Franchis
Journal: Hepatology (1992)

Little is known about the distribution of IgG–bearing cell subpopulations in normal liver and their possible changes in disease conditions. We developed an immunohistochemical method that proved suitable and accurate for the identification and characterization of IgG–bearing cells and their subpopulations in liver specimens. The method uses specific monoclonal antibodies on serial mirror liver sections. We applied this method to four normal liver tissue specimens and 25 liver biopsy samples of chronic hepatitis of viral etiology. Only rare IgG–bearing cells could be observed in the portal tracts of normal liver specimens. In contrast, a dense infiltrate of such cells was seen in liver specimens from patients with chronic viral hepatitis. The density of IgG–bearing cells in such patients ranged from 6 to 20 cells × 10 -4 μm 2 in the different specimens (x- = 11 × 10 -4 μm 2 ). The increase in IgG–bearing cells did not appear to be related to the histological diagnosis, to the degree of histological inflammatory activity or to the type of viral infection. The major population of IgG–bearing cells consisted of IgG1–positive cells (68%); IgG 2 – (17%), IgG 3 – (8%) and IgG 4 (7%)-bearing cells represented only minor fractions. The increased prevalence of IgG 1 –bearing cells observed in chronic hepatitis but not in normal liver specimens suggests that these findings may reflect an activation of antibody production directed toward viral antigens or antigenic structures of self. The identification of the antigenic specificities of the antibodies produced by IgG–bearing cells might provide important clues in understanding the pathogenesis of chronic viral hepatitis. (Hepatology 1992:16:19-23.)
Disorganized attachment and reproductive strategies
Authors: Andrew J. Lewis, Gregory Tooley
Journal: Behavioral and Brain Sciences (2009)

Abstract Del Giudice provides an extension of the life history theory of attachment that incorporates emerging data suggestive of sex differences in avoidant male and preoccupied female attachment patterns emerging in middle childhood. This commentary considers the place of disorganized attachment within this theory and why male children may be more prone to disorganized attachment by drawing on Trivers's parental investment theory.
<i>CYP24A1</i>Is an Independent Prognostic Marker of Survival in Patients with Lung Adenocarcinoma
Authors: Guoan Chen, So Hee Kim, Amanda N. King, Lili Zhao, Robert U. Simpson, Paul J. Christensen, Zhuwen Wang, Dafydd G. Thomas, Thomas J. Giordano, Lin Lin, Dean E. Brenner, David G. Beer, Nithya Ramnath
Journal: Clinical Cancer Research (2010)

Abstract Purpose: The active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25-D3), exerts antiproliferative effects in cancers, including lung adenocarcinoma (AC). CYP24A1 is overexpressed in many cancers and encodes the enzyme that catabolizes 1,25-D3. The purpose of our study was to assess CYP24A1 as a prognostic marker and to study its relevance to antiproliferative activity of 1,25-D3 in lung AC cells. Experimental Design: Tumors and corresponding normal specimens from 86 patients with lung AC (stages I–III) were available. Affymetrix array data and subsequent confirmation by quantitative real time-PCR were used to determine CYP24A1 mRNA expression. A subsequent validation set of 101 lung AC was used to confirm CYP24A1 mRNA expression and its associations with clinical variables. The antiproliferative effects of 1,25-D3 were examined using lung cancer cell lines with high as well as low expression of CYP24A1 mRNA. Results: CYP24A1 mRNA was elevated 8- to 50-fold in lung AC (compared to normal nonneoplastic lung) and significantly higher in poorly differentiated cancers. At 5 years of follow-up, the probability of survival was 42% (high CYP24A1, n = 29) versus 81% (low CYP24A1, n = 57) (P = 0.007). The validation set of 101 tumors showed that CYP24A1 was independently prognostic of survival (multivariate Cox model adjusted for age, gender, and stage, P = 0.001). A549 cells (high CYP24A1) were more resistant to antiproliferative effects of 1,25-D3 compared with SKLU-1 cells (low CYP24A1). Conclusions: CYP24A1 overexpression is associated with poorer survival in lung AC. This may relate to abrogation of antiproliferative effects of 1,25-D3 in high CYP24A1 expressing lung AC. Clin Cancer Res; 17(4); 817–26. ©2010 AACR.
Subcellular localization of the PGE2 synthesis activity in mouse resident peritoneal macrophages.
Authors: C Darte, H Beaufay
Journal: The Journal of Experimental Medicine (1984)

The aim of this work was to establish, on a quantitative basis, the subcellular distribution of the enzyme system that converts arachidonic acid into prostaglandin (PG) E2 in mouse resident peritoneal (MRP) macrophages. Kinetic studies were conducted on cell-free extracts derived from cells cultivated for 1 d, using [1-14C]arachidonic acid as substrate and measuring the label in PGE2 after extraction and thin layer chromatography. The activity was synergistically enhanced by L-adrenaline and reduced glutathione, inhibited by indomethacin, and linearly related to the concentration of the cell-free extract. It was labile at 0 degrees C in the medium used for homogenization and fractionation of the cells (half-life less than 2 h). Addition of catalase (0.15 mg/ml) to the suspension medium increased the initial activity (by congruent to 70%) and the stability (half-life congruent to 6 h) of the enzyme in cytoplasmic extracts. It enabled us to establish the density distribution after isopycnic centrifugation in a linear gradient of sucrose. The sample centrifuged consisted of untreated cytoplasmic extracts, or cytoplasmic extracts treated with digitonin and Na pyrophosphate. Comparison of the centrifugation behavior of PGE2 synthesis activity with that of various enzymes used as reference for the major subcellular entities has revealed that PGE2 synthesis fairly fits the density profile of sulfatase C in each case. The conclusion is that at least the rate-limiting reaction in the conversion of arachidonic acid into PGE2 is catalyzed by an enzyme associated with the endoplasmic reticulum.
Glycemic Control and Prognosis in Type I Diabetic Patients With Microalbuminuria
Authors: Mats Bojestig, Hans J Arnqvist, Bengt E Karlberg, Johnny Ludvigsson
Journal: Diabetes Care (1996)

OBJECTIVE To investigate the course of microalbuminuria during the 1980s in type I diabetes patients. RESEARCH DESIGN AND METHODS This was a 10-year follow-up of 109 patients in whom type I diabetes was diagnosed between 1961 and 1980 before 15 years of age and who were initially investigated between 1977 and 1983 after a diabetes duration of ≥ 3 years. Microalbuminuria was defined as an albumin excretion rate (AER) of 20-200 μg/min in two of three consecutive urine samples. RESULTS At the initial investigation, 81 patients had normal AER, 27 had microalbuminuria, and 1 had macroalbuminuria. Between 1989 and 1992, 99 (91%) patients were reinvestigated. Only 5 (19%) of the initially microalbuminuric patients developed macroproteinuria during the 10-year follow-up period, and in 15 (58%) patients, AER decreased to normal. Three (4%) of the normoalbuminuric patients developed microalbuminuria but none macroproteinuria. The initially microalbuminuric patients, in whom AER normalized, improved their glycemic control from 1980-1983 to 1989-1991 (mean ± SE HbA1c 7.5 ± 0.2 to 6.6 ± 0.3%; P = 0.01). CONCLUSIONS In the majority of patients with microalbuminuria in whom it is possible to obtain good glycemic control, microalbuminuria will disappear and the risk of developing nephropathy will be markedly reduced.
Analysis of heart rate variability at rest and during aerobic exercise: a study in healthy people and cardiac patients
Authors: B de la Cruz Torres, C López López, J Naranjo Orellana
Journal: British Journal of Sports Medicine (2008)

To analyse HRV at rest in healthy people and in patients with acute myocardial infarction (AMI) and how it changes during aerobic exercise.The heartbeat signal was recorded beat to beat for 15 minutes at rest and 15 minutes while pedalling in 10 healthy and active men (H group) and 10 cardiac patients (C group). The statistical parameters in the time domain were calculated as well as the spectral analysis applying the Fast Fourier Transform (FFT) and Poincare's graphic analysis (PGA).At rest, H group have an average SDRR (standard deviation of RR intervals) of 71.24 msec, a pRR50 (percentage of differences higher than 50 msec in RR intervals) of 9.97% and a PGA called "comet-type". The C group have a SDRR of 36.69 msec, a pRR50 of 1.69%, and a PGA "torpedo-type". These data show a low or moderate risk for healthy people and a high risk for patients. The FFT analysis lies in the very-low-frequency (VLF) zone in both groups. During exercise, H group shows a significant decrease in all parameters; the PGA turns to "torpedo-type" and the FFT remains in the VLF zone. However, C group is characterised by the maintenance of pRR50, no change in PGA and a second peak in FFT in the high-frequency zone.The HRV at rest and during aerobic exercise follows a different pattern in healthy people and in patients and it provides further information about performance during exercise.
Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis
Authors: P M van Grunsven, C P van Schayck, J P Derenne, H A M Kerstjens, T E J Renkema, D S Postma, T Similowski, R P Akkermans, P C M P.-d. Jong, P N R Dekhuijzen, C L A van Herwaarden, C van Weel
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The role of inhaled corticosteroids in the long term management of chronic obstructive pulmonary disease (COPD) is still unclear. A meta-analysis of the original data sets of the randomised controlled trials published thus far was therefore performed. The main question was: “Are inhaled corticosteroids able to slow down the decline in lung function (FEV<sub>1</sub>) in COPD?” <h3>METHODS</h3> A Medline search of papers published between 1983 and 1996 was performed and three studies were selected, two of which were published in full and one in abstract form. Patients with “asthmatic features” were excluded from the original data. Ninety five of the original 140 patients treated with inhaled corticosteroids (81 with 1500 μg beclomethasone daily, six with 1600 μg budesonide daily, and eight with 800 μg beclomethasone daily) and 88 patients treated with placebo (of the initial 144 patients) were included in the analysis. The effect on FEV<sub>1</sub> was assessed by a multiple repeated measurement technique in which points of time in the study and treatment effects (inhaled corticosteroids compared with placebo) were investigated. <h3>RESULTS</h3> No baseline differences were observed (mean age 61 years, mean FEV<sub>1</sub>45% predicted). The estimated two year difference in prebronchodilator FEV<sub>1</sub> was +0.034 l/year (95% confidence interval (CI) 0.005 to 0.063) in the inhaled corticosteroid group compared with placebo. The postbronchodilator FEV<sub>1</sub> showed a difference of +0.039 l/year (95% CI –0.006 to 0.084). No beneficial effect was observed on the exacerbation rate. Worsening of the disease was the reason for drop out in four patients in the treatment group compared with nine in the placebo group. In the treatment group six of the 95 subjects dropped out because of an adverse effect which may have been related to the treatment compared with two of the 88 patients in the placebo group. <h3>CONCLUSIONS</h3> This meta-analysis in patients with clearly defined moderately severe COPD showed a beneficial course of FEV<sub>1</sub> during two years of treatment with relatively high daily dosages of inhaled corticosteroids.
THE PATTERN OF FOOD AND MORTALITY IN BELGIUM
Authors: J.V Joossens, E Brems-Heyns, J.H Claes, M Graffar, M Kornitzer, R Pannier, O Van Houte, K Vuylsteek, J Carlier, G De Backer, H Kesteloot, J Lequime, A Raes, M Vastesaeger, G Verdonk
Journal: The Lancet (1977)
Reports recommend shorter training for hospital doctors and longer training for GPs in Scotland
Authors: Bryan Christie
Journal: BMJ (2004)

The government's Social Exclusion Unit (SEU) has announced far-reaching proposals which it hopes will end the stigma and discrimination attached to mental illness and encourage people back into meaningful lives.This week the unit launched its report, Mental Health and Social Exclusion, which calls for health services to focus on the social as well as medical needs of hundreds of thousands of people excluded from wider society by mental illness.The report sets out a five year plan with an ambitious antistigma and discrimination campaign aimed at employers, schools, and the media, which it hopes will dispel cultural myths that people with mental illness are dangerous, unstable, and unemployable.All psychiatric patients in hospital are to be given vocational advice and support, and trusts will be told to strengthen links with job centres.NHS day centres must be redesigned with a focus on re-integrating patients into the community via job training, advice about employment, education, or voluntary work.
The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease
Authors: John Steer, John Gibson, Stephen C Bourke
Journal: Thorax (2012)

<h3>Background</h3> Despite exacerbations of chronic obstructive pulmonary disease (COPD) being both common and often fatal, accurate prognostication of patients hospitalised with an exacerbation is difficult. For exacerbations complicated by pneumonia, the CURB-65 prognostic tool is frequently used but its use in this population is suboptimal. <h3>Methods</h3> Consecutive patients hospitalised with an exacerbation of COPD were recruited. Admission clinical data and inhospital death rates were recorded. Independent predictors of outcome were identified by logistic regression analysis and incorporated into a clinical prediction tool. <h3>Results</h3> 920 patients were recruited: mean (SD) age was 73.1 (10.0) years; 53.9% were female subjects; mean (SD) forced expiratory volume in one second was 43.6 (17.2) % predicted; and 96 patients (10.4%) died in hospital. The five strongest predictors of mortality (extended MRC Dyspnoea Score, eosinopenia, consolidation, acidaemia, and atrial fibrillation) were combined to form the Dyspnoea, Eosinopenia, Consolidation, Acidaemia and atrial Fibrillation (DECAF) Score. The Score, which underwent internal bootstrap validation, showed excellent discrimination for mortality (area under the receiver operator characteristic curve =0.86, 95% CI 0.82 to 0.89) and performed more strongly than other clinical prediction tools. In the subgroup of patients with coexistent pneumonia (n=299), DECAF was a significantly stronger predictor of mortality than CURB-65. <h3>Conclusions</h3> The DECAF Score is a simple yet effective predictor of mortality in patients hospitalised with an exacerbation of COPD and has the potential to help clinicians more accurately predict prognosis, and triage place and level of care to improve outcome in this common condition.
A novel mouse model of veno-occlusive disease provides strategies to prevent thioguanine-induced hepatic toxicity
Authors: Iulia Oancea, Chin Wen Png, Indrajit Das, Rohan Lourie, Ingrid G Winkler, Rajaraman Eri, Nathan Subramaniam, H A Jinnah, Brett C McWhinney, Jean-Pierre Levesque, Michael A McGuckin, John A Duley, Timothy H J Florin
Journal: Gut (2012)

<h3>Objective</h3> The anti-leukemic drugs, azathioprine and 6-mercaptopurine (6MP), are important in the treatment of inflammatory bowel disease but an alternative faster-acting, less-allergenic thiopurine, 6-thioguanine (6TG), can cause hepatic veno-occlusive disease/sinusoidal obstructive syndrome (SOS). Understanding of SOS has been hindered by inability to ethically perform serial liver biopsies on patients and the lack of an animal model. <h3>Design</h3> Normal and C57Bl/6 mice with specific genes altered to elucidate mechanisms responsible for 6TG-SOS, were gavaged daily for upto 28d with 6TG, 6MP or methylated metabolites. Animal survival was monitored and at sacrifice a histological score of SOS, haematology and liver biochemistry were measured. <h3>Results</h3> Only 6TG caused SOS, which was dose related. 6TG and to a lesser extent 6MP but not methylated metabolites were associated with dose-dependent haematopoietic toxicity. SOS was not detected with non-lethal doses of 6TG. SOS did not occur in hypoxanthine-phosphoribosyl transferase<i>-</i>deficient C57Bl/6 mice, demonstrating that 6TG-SOS requires thioguanine nucleotides. Hepatic inflammation was characteristic of SOS, and C57Bl/6 mice deficient in P- and E-selectins on the surface of vascular endothelial cells showed markedly reduced SOS, demonstrating a major role for leukocytes recruited from blood. Split dosing of 6TG markedly attenuated SOS but still effected immunosuppression and prevented spontaneous colitis in <i>Winnie</i> mice, which have a single nucleotide polymorphism mutation in <i>Muc2</i>. <h3>Conclusion</h3> This novel model provides clinically relevant insights into how 6TG induces SOS, and how this dangerous adverse drug reaction may be avoided by either inhibition of endothelial activation or simple changes to dosing regimens of 6TG, while still being effective treatment for colitis.
The Birth of the Subspecialty of Medical Oncology and Examples of Its Early Scientific Foundations
Authors: Pierre R. Band
Journal: Journal of Clinical Oncology (2010)

“Passion is not accepting defeat.” —Emil Frei III In the early 1950s, an experimental and clinical program characterized by unique cross-fertilization was developed. The clinical importance of experimental animal models in drug screening and in establishing key chemotherapy concepts and the role of the pioneers of medical oncology in the design of the various phases of drug trials, using childhood acute leukemia and breast cancer as models, are discussed. Over a short time and with only a few drugs, principles of chemotherapy were laid out, which led to cures in such diseases as childhood acute leukemia and Hodgkin's disease and to improved disease-free survival in breast cancer. It is these and other achievements that paved the way to medical oncology. At the instigation of the American Society of Clinical Oncology (ASCO), the American Board of Internal Medicine made inquiries about a subspecialty in oncology. ASCO and B. J. Kennedy, MD, played key roles in the events leading to the official recognition of medical oncology as a new subspecialty of internal medicine in 1972.
Low Prevalence of Subclinical Atherosclerosis in Asymptomatic Patients With Type 1 Diabetes in a European Mediterranean Population
Authors: Eva Aguilera, Enric Serra-Planas, M. Luisa Granada, Núria Alonso, Silvia Pellitero, Eduarda Pizarro, Jordi Lluís Reverter, Isabel Salinas, Berta Soldevila, Dídac Mauricio, Manel Puig-Domingo
Journal: Diabetes Care (2013)

To evaluate the presence of early carotid and coronary atherosclerosis in asymptomatic patients with type 1 diabetes with no history of ischemic heart disease.One hundred and fifty patients with type 1 diabetes (58% males; 38.6 ± 8.1 years, 20.4 ± 8.1 years of evolution; HbA1c 8.1 ± 2.3%; 52% nonsmokers; 26% retinopathy; 9% microalbuminuria) and 50 nondiabetic control subjects age and sex matched were studied. Carotid ultrasonography to determine common carotid artery intima-media thickness (c-IMT) and the presence of atheroma plaques and cardiac computed tomography for calcium analysis and quantification (coronary artery calcium score [CACS]) were performed.Most patients with type 1 diabetes and control subjects displayed a CACS of 0 (82 vs. 92%). Patients with type 1 diabetes with CACS ≥1 were older and had higher HbA1c (44.5 ± 5.1 vs. 36.7 ± 8.1 years [P < 0.001] and 8.5 ± 1.1 vs. 7.8 ± 1.0% [P < 0.003], respectively) and longer evolution of diabetes (25.4 ± 9.2 vs. 19.3 ± 7.4 years, P < 0.005) and mean c-IMT (0.67 ± 0.18 vs. 0.53 ± 0.11 mm, P < 0.001) compared with patients with CACS of 0. Smoking (P < 0.02), nephropathy (P < 0.05), retinopathy (P < 0.05), and male sex (P < 0.03) were significantly and positively associated with CACS ≥1. Mean c-IMT was significantly higher in patients with type 1 diabetes (0.55 ± 0.14 vs. 0.48 ± 0.14 mm, P < 0.01), and 11% of them presented atheroma plaques (8% of control subjects). Multivariant logistic regression analysis showed that c-IMT was related to CACS (β = 6.87, P < 0.001).A small percentage of patients with type 1 diabetes showed data suggestive of subclinical atherosclerosis. Universal screening of coronary disease in this population is not justified. Carotid ultrasonography may be useful for screening in the subset of patients with cardiovascular risk factors and long disease evolution.
Cerebral thrombosis in a newborn with a congenital deficiency of antithrombin III
Authors: B. Brenner, A. Fishman, D. Goldsher, D. Schreibman, S. Tavory
Journal: American Journal of Hematology (1988)

Abstract An Israeli Arab family with type I antithrombin III (AT‐III) deficiency with several affected symptomatic members in three generations is reported. The propositus presented with deep vein thrombosis and pulmonary emboli associated with gestation. The propositus infant presented at the age of 2 weeks with superior sagittal and rectus sinus thrombosis. Hereditary AT‐III deficiency should be considered in infants with cerebral thrombosis, especially if they have a family history of thromboembolism. The role of prophylactic therapy by AT‐III concentrates in these infants should be further assessed.
The effects of ketolides on bioactive phospholipid-induced injury to human respiratory epithelium in vitro
Authors: C. Feldman, R. Anderson, A Theron, I Mokgobu, P.j Cole, R Wilson
Journal: European Respiratory Journal (1999)

The potential of the novel ketolide antimicrobial agents, HMR 3004 and HMR 3647, to antagonize the injurious effects of the bioactive phospholipids (PL), platelet-activating factor (PAF), lyso-PAF, and lysophosphatidylcholine (LPC) on the ciliary beat frequency and structural integrity of human ciliated respiratory epithelium in vitro was investigated, in the presence or absence of polymorphonuclear leukocytes (PMNL). The ciliary beat frequency of human nasal respiratory epithelium, obtained by nasal brushing of healthy volunteers, was measured using a photo-transistor technique, while superoxide generation by activated human PMNL and membrane-stabilizing activity were measured by lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively. All three PL, at concentrations of 2.5 microg x mL(-1), caused significant (p<0.005) ciliary slowing and epithelial damage, while treatment of the epithelial strips with the ketolides, in particular HMR 3004, caused dose-related attenuation of these direct adverse effects of the PL on ciliated epithelium, apparently by a membrane-stabilizing mechanism. When epithelial strips were exposed to the combination of PMNL (1 x 10(6) cells x mL(-1)) and PAF (1 microg x mL(-1)), significant ciliary dysfunction and epithelial damage were also observed, which were mediated predominantly by neutrophil-derived oxidants. These injurious effects of PAF were antagonized by preincubation of the epithelial strips or the PMNL with HMR 3004 (10 microg x mL(-1)). The ketolide antimicrobial agents, in particular HMR 3004, antagonize the direct and polymorphonuclear leukocyte-mediated injurious effects of phospholipids on human ciliated epithelium and may have beneficial effects in inflammatory disorders of the airways, such as asthma, chronic bronchitis, diffuse panbronchiolitis and bronchiectasis.