tbuckley/cabot-search huggingface dataset:
Suicide in patients with stroke: epidemiological study
Authors: E. N. Stenager, C. Madsen, E. Stenager, J. Boldsen
Journal: BMJ (1998)

In the United States stroke is the third most common cause of death among those aged over 70. In Europe the incidence of stroke is 2 per 1000 population a year.1 Survivors are often incapacitated. The frequency of depression after stroke is estimated at 18-60%.2 Other neurological disorders that may result in mental and cognitive disorders are associated with an increased risk of suicidal behaviour.3 Studies on the possible increased risk of suicide among patients with stroke have never been performed. We therefore aimed to estimate, on the basis of a cohort of patients with stroke in a selected area in Denmark, whether the risk of suicide was higher than in the background population (the common reference in previous studies on suicide risk).

All patients admitted to hospital in the county of Funen, Denmark, with a discharge diagnosis of stroke (code 430-438 according …
Sympathetic nervous system-dependent vasoconstriction in humans. Evidence for mechanistic role of endogenous purine compounds.
Authors: S Taddei, R Pedrinelli, A Salvetti
Journal: Circulation (1990)

Purine compounds modulate sympathetic neurotransmission; this modulation decreases nervous discharge by stimulating presynaptic inhibitory adenosine receptors, an effect antagonized by theophylline, and causes vasoconstriction through the stimulation of postsynaptic ATP receptors. In humans we evaluated the effect of local theophylline, which was infused into the brachial artery at the rate of 100 micrograms/100 cc/min, on the arteriolar sympathetic vasoconstriction induced by applying a lower-body negative pressure. Forearm blood flow changes were measured by strain-gauge venous plethysmography. Theophylline, which at this dosage blunted the vasodilator effect of adenosine (the physiological agonist for the P1 purinoceptor), significantly increased lower-body negative pressure-mediated vasoconstriction. To evaluate whether neurotransmitters different from norepinephrine participate in the vasoconstrictor effect of theophylline, we repeated the previous experiment in the presence of phenoxybenzamine, which was infused at a dose (60 micrograms/100 cc/min) that abolished the vasoconstrictor effect of norepinephrine. Also, after alpha-adrenoceptor blockade, theophylline continued to increase sympathetic vasoconstriction. Our data confirm that purinergic receptors and neurotransmitters also participate in endogenous sympathetic vasoconstriction in humans.
The Novel Triterpenoid C-28 Methyl Ester of 2-Cyano-3, 12-Dioxoolen-1, 9-Dien-28-Oic Acid Inhibits Metastatic Murine Breast Tumor Growth through Inactivation of STAT3 Signaling
Authors: Xiaoyang Ling, Marina Konopleva, Zhihong Zeng, Vivian Ruvolo, L. Clifton Stephens, Wendy Schober, Teresa McQueen, Martin Dietrich, Timothy L. Madden, Michael Andreeff
Journal: Cancer Research (2007)

Abstract We and others have reported that C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid (CDDO-Me) effectively inhibits the growth of multiple cancer cell types. Our previous studies indicated that prolonged CDDO-Me treatment inactivated extracellular signal-regulated kinase signaling in acute myelogenous leukemia cells. Whether treatment with CDDO-Me has an earlier effect on other proteins that are important for either signal transduction or oncogenesis is unknown. Constitutively activated signal transducer and activator of transcription 3 (STAT3) is frequently found in human breast cancer samples. Constitutively activated STAT3 was shown to up-regulate c-Myc in several types of cancer and has a feedback effect on Src and Akt. To examine the effects of CDDO-Me on STAT3 signaling in breast cancer, we used the murine 4T1 breast tumor model, which is largely resistant to chemotherapy. In vitro, after treatment of 4T1 cells with 500 nmol/L CDDO-Me for 2 h, we found (a) inactivation of STAT3, (b) inactivation of Src and Akt, (c) 4-fold reduction of c-Myc mRNA levels, (d) accumulation of cells in G2-M cell cycle phase, (e) abrogation of invasive growth of 4T1 cells, and (f) lack of apoptosis induction. In in vivo studies, CDDO-Me completely eliminated 4T1 breast cancer growth and lung metastases induced by 4T1 cells in mice when treatment started 1 day after tumor implantation and significantly inhibited tumor growth when started after 5 days. In vivo studies also indicated that splenic mature dendritic cells were restored after CDDO-Me treatment. In summary, these data suggest that CDDO-Me may have therapeutic potential in breast cancer therapy, in part, through inactivation of STAT3. [Cancer Res 2007;67(9):4210–17]
THE IMMUNOLOGICAL BEHAVIOUR OF THE SECOND PROTEIN (LIVETIN) OF HEN'S EGG YOLK
Authors: T. H. Jukes, H. D. Kay
Journal: The Journal of Experimental Medicine (1932)

A comparison of the livetin of egg yolk and serum globulin of the common fowl using (a) anaphylactic and (b) precipitin reactions, indicates that the two proteins are very closely related, if not identical. The complement fixation test does not give the same result but indicates a difference between the two proteins. The complement fixation test also shows differences between serum euglobulin and serum pseudoglobulin when these proteins, prepared with considerable care, cannot be distinguished either by anaphylactic or precipitin tests.
Bleeding complications after pleural procedures in patients on antiplatelet therapy: A French survey
Authors: Laurence Dangers, Thomas Similowski, Cécile Chenivesse
Journal: European Respiratory Journal (2013)

Introduction. When pleural procedures (PP) are required in patients receiving antiplatelet therapy (APT), the increased risk of bleeding complications associated with APT must be balanced against the risk of thrombosis after APT withdrawal. However the risk of bleeding after pleural procedures in patients on APT is unknown. Therefore, practices are considerably heterogeneous.

Objectives. To investigate the opinion of French Pulmonologists regarding the bleeding risk related to APT after PP.

Methods. A questionnaire was emailed to 2011 French Pulmonologists.

Results. 184 questionnaires have been collected (response rate 9,1%; completion rate 95%). Pulmonologists proceeded to an average of 8 PP per month and 175 (95%) were performing PP in patients receiving APT. They were more hesitant in performing PP in patients on clopidogrel than in patients on aspirin (thoracocentesis: 24% versus 3%, blind pleural biopsy: 93% versus 50%, chest tube insertion: 58% versus 13%, p<0,001). The risk of bleeding was considered minor for thoracocentesis (97% of opinions) and chest tube insertion (64% of opinions) and major for blind pleural biopsy (74% of opinions).

Conclusions. We report the first data about the bleeding risk of PP in patients on APT through a French opinion survey. Practicing physicians consider that receiving clopidogrel represents a higher risk than receiving aspirin in the perspective of pleural procedures. This should be verified by observational studies.
Nonionic Polymers Reverse Inactivation of Surfactant by Meconium and Other Substances
Authors: H. WILLIAM TAEUSCH, KAREN W. LU, JON GOERKE, JOHN A. CLEMENTS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

A variety of substances including human meconium have been found to affect adversely the surface tension-lowering activity of pulmonary surfactants, and this effect may be important in the pathogenesis of a number of human diseases. To find whether inactivation of surfactant could be prevented or reduced by nonionic polymers, we added dextrans, polyethylene glycols (PEGs), or polyvinylpyrrolidones (PVPs) of various molecular weights to pulmonary surfactants. One to 3% human meconium or other inactivating substances were then added to the mixtures, which were tested in a modified pulsating bubble surfactometer. Polymers (3.3-500 kD) in 1-10% concentrations enhanced the ability of a commercial surfactant replacement (Survanta) to lower the minimum surface tension in the presence of meconium, serum, or lysophosphatidylcholine. Similar effects were seen when polymers were added after mixing of surfactant and meconium or other inhibitors, indicating that polymers are capable of reversing the inactivation. Results from rat experiments indicate that total lung capacity is increased when PEG is first added to the Survanta, then mixed with meconium and instilled into the lungs. We postulate that polymers separate meconium-surfactant complexes, permitting surfactant components better access to the air-liquid interface. Taeusch HW, Lu KW, Goerke J, Clements JA. Nonionic polymers reverse inactivation of surfactant by meconium and other substances.
Investigation of C reactive protein gene polymorphisms as predictors of cardiovascular mortality in inflammatory polyarthritis: results from the Norfolk Arthritis Register: Table 1
Authors: Ibrahim Ibrahim, Darren Plant, Mark Lunt, Suzanne Verstappen, Edward Flynn, Deborah Symmons, Anne Barton
Journal: Annals of the Rheumatic Diseases (2013)

Patients with rheumatoid arthritis (RA) and inflammatory polyarthritis (IP) are at increased risk of premature death, with cardiovascular disease (CVD) forming the primary cause.1–3 However, epidemiological studies have shown that traditional CVD risk factors do not fully account for the increased risk.4 ,5

We have previously reported that IP patients with baseline C reactive protein (CRP) concentrations ≥5 mg/l are at greatest risk of CVD mortality.6 Previous studies have shown that single nucleotide polymorphisms (SNPs) at the CRP gene correlate with CRP levels in a healthy population,7 and haplotypes of these SNPs are associated with CRP levels following acute coronary syndrome.8 Therefore, if CRP SNPs/haplotypes were associated with CVD in individuals with IP, it would implicate CRP in the pathogenesis of CVD (Mendelian randomisation).

The aims of this study were (1) to determine the relationship between SNP markers (rs1205, rs1800947 and rs3091244) in the CRP gene, selected …
The separation of alpha-2 macroglobulin into five components with differing electrophoretic and enzyme-binding properties
Authors: Russell Saunders, Barbara J. Dyce, Wilton E. Vannier, Bernard J. Haverback
Journal: Journal of Clinical Investigation (1971)

The alpha-2 macroglobulins from human serum and plasma were isolated by Bio-Gel P-300 and A5m gel filtration. The material showed a single peak on sedimentation velocity ultracentrifugation, a mol wt of 650,000 by sedimentation equilibrium ultracentrifugation, and a major precipitin arc in the alpha-2 macroglobulin region by immunoelectrophoresis against whole human serum. Two bands were observed in the alpha-2 macroglobulin region when acrylamide gel electrophoresis was performed with a pH 8.9 running gel. When a pH 7.8 gel was used, five electrophoretic species were observed. In both cases, the preaddition of stoichiometric amounts of trypsin or chymotrypsin added to alpha-2 macroglobulin resulted in disappearance of slower bands leaving only one band on acrylamide gel electrophoresis patterns. Preparative acrylamide gel electrophoresis separated alpha-2 macroglobulin obtained from Bio-Gel into five closely-spaced species. Separation was sufficiently adequate to show that those species of alpha-2 macroglobulin which bound trypsin and chymotrypsin were represented by slower moving species and that the fastest moving material had lost virtually all of the ability to bind these enzymes. Preparative acrylamide gel electrophoresis of a mixture of alpha-2 macroglobulin-trypsin complex and alpha-2 macroglobulin revealed that the fast moving component was alpha-2 macroglobulin-trypsin complex and that the slower moving material was unbound alpha-2 macroglobulin. The naturally occurring amidase activity of the alpha-2 macroglobulin using benzoylarginine-p-nitroanilide (BAPNA) as substrate was investigated and unlike its trypsin-binding activity, amidase activity was found to be of the same specific activity in all electrophoretic fractions. Binding of trypsin and chymotrypsin to alpha-2 macroglobulin revealed that alpha-2 macroglobulin maximally bound 2 moles of trypsin and 1 mole of chymotrypsin. When the enzymes were added simultaneously there was competition. Chymotrypsin added to alpha-2 macroglobulin before the addition of trypsin prevented all trypsin binding even though only one site was filled with chymotrypsin. These results were explained by the acrylamide gels which showed that 1 mole of chymotrypsin was sufficient to convert all the alpha-2 macroglobulin to a species with the fastest mobility which no longer binds additional enzyme.
Evaluation of anti-citrullinated filaggrin antibodies as hallmarks for the diagnosis of rheumatic diseases
Authors: S Dubucquoi
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established. <b>Objective:</b> To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis. <b>Methods:</b> Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients. <b>Results:</b> Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to ~50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis. <b>Conclusions:</b> Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.
Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study)
Authors: F De Vita, F Giuliani, M Orditura, E Maiello, G Galizia, N Di Martino, F Montemurro, G Cartenì, L Manzione, S Romito, V Gebbia, F Ciardiello, G Catalano, G Colucci
Journal: Annals of Oncology (2007)
Voluntary decrease in breathing frequency in exercising asthmatic subjects
Authors: F Ceugniet, F Cauchefer, J Gallego
Journal: European Respiratory Journal (1996)

Exercise rehabilitation programmes are increasingly recommended in young asthmatics, but it is unclear whether or not training should incorporate instructions on breathing pattern. In this study, we examined the effects of voluntarily decreasing breathing frequency on their ventilatory equivalents for oxygen and carbon dioxide (minute ventilation (V'E)/oxygen consumption (V'O2) and V'E/CO2 production (V'CO2), respectively), noninvasively determined physiological dead space/tidal volume (VD/VT) and dyspnoea. Fifteen young asthmatic subjects were assigned to two groups: low frequency breathing (LFB) and controls. They first underwent an exercise test at a cardiac frequency of 150 beats x min(-1). They were trained at this level for nine sessions. LFB subjects were instructed to decrease respiratory frequency by 40% during exercise. Control subjects received no instructions. A second test was then performed in the same conditions. LFB subjects decreased V'E/V'O2, V'E/V'CO2 and VD/VT by 22, 19 and 12%, respectively. Arterial oxygen saturation (Sa,O2) fell to 89+/-4% and end-tidal carbon dioxide tension (PET,CO2) rose to 6.5+/-0.7 kPa (49+/-5 mmHg). In controls, these variables were identical in the two tests. Dyspnoea was lower in the second test in all subjects. In conclusion, breathing pattern may be profoundly altered during exercise without concomitant increase in dyspnoea. However, directing breathing patterns for exercise rehabilitation requires an individual assessment of the desired pattern in order to prevent hypercapnia or hypoxia.
Murine Peyer's patch T cell clones. Characterization of antigen-specific helper T cells for immunoglobulin A responses.
Authors: H Kiyono, J R McGhee, L M Mosteller, J H Eldridge, W J Koopman, J F Kearney, S M Michalek
Journal: The Journal of Experimental Medicine (1982)

We successfully cloned antigen-specific T cells from murine gut-associated lymphoreticular tissue, i.e., Peyer's patches, which are dependent upon T cell growth factor and independent of antigen for continuous growth. These clones exhibit helper activity for IgA responses to sheep erythrocytes (SRBC) and have been designated T helper (Th) A. Two broad categories of Th A clones have been maintained in continuous culture. The first group supports IgM and largely IgA anti-SRBC plaque-forming cell (PFC) responses in both normal and SRBC-primed splenic B cell cultures, whereas the second group supports low IgM, IgG1, and IgG2 and high IgA PFC responses. Subclones derived from single cells maintain the parent helper properties when propagated in culture for long periods (greater than 7 mo). Cloned Th A cells are antigen specific and do not support polyclonal or immune responses to other thymus dependent antigens in normal B cell cultures. Th A cells require full histocompatibility for helper functions because addition of cloned Th A cells to B cell cultures from other H-2 types does not result in IgA responses. Cloned Th A cells are Thy-1.2+ and Lyt-1+ and Lyt-2-, Ig-, and I-A-. Th A cells bear Fc receptors for IgA and do not possess receptors for IgM or IgG isotypes. Thus, T cells that primarily promote IgA isotype responses have been isolated in high frequency from murine PP, an anatomical site of major importance for induction and regulation of the IgA response.
Factors influencing postoperative recurrence of Crohn's disease in childhood.
Authors: A M Griffiths, D E Wesson, B Shandling, M Corey, P M Sherman
Journal: Gut (1991)

We have reviewed the outcome of all patients undergoing their first intestinal resection for Crohn9s disease at this hospital between 1970 and 1987. Recurrence rates, defined by recurrent intestinal symptoms and radiological confirmation of mucosal disease, were calculated using survival analysis. Age, sex, anatomical location of disease, indication for surgery, preoperative duration of symptomatic disease, use of preoperative bowel rest, and pathological features of the resected bowel were analysed individually and jointly as potential risk factors influencing postoperative recurrence of disease. Eighty two patients (age, mean (SD) 14.8 (2.5) years) underwent intestinal resection and were followed postoperatively for a minimum of one year (mean 5.3 (3.3) years). Anatomical location of disease, indication for surgery, and preoperative duration of symptomatic disease were the only factors that significantly influenced the duration of the recurrence free interval. Patients with diffuse ileocolonic inflammation experienced earlier recurrence (50% at one year) than children with predominantly small bowel disease (50% recurrence at five years, p less than 0.0001). Failure of medical therapy independent of disease location as the sole indication for surgery was associated with an earlier relapse than when surgery was performed for a specific intestinal complication such as abscess or obstruction (p less than 0.003). Patients undergoing resection within one year of onset of symptoms experienced delayed recrudescence of active disease (30% recurrence by eight years) compared with patients whose preoperative duration of symptomatic disease was longer (50% recurrence by four years when preoperative duration of disease was one to four years and 50% by three years when disease had been present greater than four years preoperatively, p = 0.03). The mean height velocity of patients with growth potential increased from 2.4 (2.3) cm per year preoperatively to 8.1 (3.4) cm per year in the first postoperative year (p=0.0001). These results support an early approach to surgery in the management of ileal Crohn9s disease with or without caecal or right colonic involvement, especially when complicated by persistent growth failure. The higher recurrence rates in more diffuse ileocolonic disease emphasise the need for alternative treatment strategies in these children.
Mechanism of Action of the Nongenotoxic Peroxisome Proliferators: Role of the Peroxisome Proliferator-Activated Receptor 
Authors: F. J. Gonzalez, J. M. Peters, R. C. Cattley
Journal: JNCI Journal of the National Cancer Institute (1998)

Peroxisome proliferators are a diverse group of chemicals that include several therapeutically used drugs (e.g., hypolipidemic agents), plasticizers and organic solvents used in the chemical industry, herbicides, and naturally occurring hormones. As the name implies, peroxisome proliferators cause an increase in the number and size of peroxisomes in the liver, kidney, and heart tissue of susceptible species, such as rats and mice. Long-term administration of peroxisome proliferators can cause liver cancer in these animals, a response that has been the central issue of research on peroxisome proliferators for many years. Peroxisome proliferators are representative of the class of nongenotoxic carcinogens that cause cancer through mechanisms that do not involve direct DNA damage. The fact that humans are frequently exposed to these agents makes them of particular concern to government regulatory agencies responsible for assuring human safety. Whether frequent exposure to peroxisome proliferators represents a hazard to humans is unknown; however, increased cancer risk has not been shown to be associated with long-term therapeutic administration of the hypolipidemic drugs gemfibrozil, fenofibrate, and clofibrate. To make sound judgments regarding the safety of peroxisome proliferators, the validity of extrapolating results from rodent bioassays to humans must be based on the agents' mechanism of action and species differences in biologic activity and carcinogenicity. The peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily, has been found to mediate the activity of peroxisome proliferators in mice. Gene-knockout mice lacking PPARalpha are refractory to peroxisome proliferation and peroxisome proliferator-induced changes in gene expression. Furthermore, PPARalpha-null mice are resistant to hepatocarcinogenesis when fed a diet containing a potent nongenotoxic carcinogen WY-14,643. Recent studies have revealed that humans have considerably lower levels of PPARalpha in liver than rodents, and this difference may, in part, explain the species differences in the carcinogenic response to peroxisome proliferators.