tbuckley/cabot-search huggingface dataset:
Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor Simvastatin Prevents Cardiac Hypertrophy Induced by Pressure Overload and Inhibits p21 <i>ras</i> Activation
Authors: Ciro Indolfi, Emilio Di Lorenzo, Cinzia Perrino, Angela Maria Stingone, Antonio Curcio, Daniele Torella, Antonello Cittadini, Luca Cardone, Carmela Coppola, Luigi Cavuto, Oreste Arcucci, Luigi Sacca, Enrico Vittorio Avvedimento, Massimo Chiariello
Journal: Circulation (2002)

Patients with cardiac hypertrophy are at increased cardiovascular risk. It has been hypothesized that hydroxymethylglutaryl coenzyme A reductase inhibitors may exert beneficial effects other than their cholesterol-lowering actions. The aims of the study were to assess the in vivo effects of simvastatin (SIM) on cardiac hypertrophy and on Ras signaling in rats with ascending aorta banding.Wistar rats were randomized to receive either treatment with SIM or placebo, and then short-term (group I) and long-term (group II) left ventricular pressure overload was performed by placing a tantalum clip on ascending aorta. At the end of treatment period, left and right ventricular weight, body weight, and tibial length were measured and echocardiographic evaluations were performed. Ras signaling was investigated by analyzing Ras membrane localization and activation, ERK2 phosphorylation, and p27(kip1) and cdk4 levels. In SIM-treated rats, a significant reduction of left ventricular weight/body weight, echocardiographic left ventricular mass, and left ventricular end-diastolic diameter and end-diastolic pressure was found. In rats with pressure overload, SIM treatment significantly reduced Ras membrane targeting, Ras in vivo activation, ERK2 phosphorylation, and the ratio cdk4/p27(kip1).HMG CoA inhibitor SIM inhibits in vivo Ras signaling and prevents left ventricular hypertrophy development in aortic-banded animals.
Critical Role for Fas-Associated Death Domain-Like Interleukin-1-Converting Enzyme-Like Inhibitory Protein in Anoikis Resistance and Distant Tumor Formation
Authors: I. A. Mawji, C. D. Simpson, R. Hurren, M. Gronda, M. A. Williams, J. Filmus, J. Jonkman, R. S. Da Costa, B. C. Wilson, M. P. Thomas, J. C. Reed, G. V. Glinsky, A. D. Schimmer
Journal: JNCI Journal of the National Cancer Institute (2007)

Normal epithelial cells undergo anoikis, or apoptosis on loss of anchorage to the extracellular matrix, by initiating the death receptor pathway of caspase activation. However, malignant epithelial cells with metastatic potential resist anoikis and can survive in an anchorage-independent fashion. We hypothesized that c-Fas-associated death domain-like interleukin-1-converting enzyme-like inhibitory protein (FLIP), an endogenous inhibitor of death receptor signaling, may suppress anoikis.
Use of complementary and alternative medicine in cancer patients: a European survey
Authors: A. Molassiotis, P. Fernadez-Ortega, D. Pud, G. Ozden, J.A. Scott, V. Panteli, A. Margulies, M. Browall, M. Magri, S. Selvekerova, E. Madsen, L. Milovics, I. Bruyns, G. Gudmundsdottir, S. Hummerston, A. M.-A. Ahmad, N. Platin, N. Kearney, E. Patiraki
Journal: Annals of Oncology (2005)
Effects of nitrogen dioxide exposure and ascorbic acid supplementation on exhaled nitric oxide in healthy human subjects
Authors: D C Chambers
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Nitric oxide (NO) is detectable in the exhaled breath, is involved in airway defence and inflammation, and probably modulates bronchial smooth muscle tone. Given the sensitivity of nitrogen oxides to local redox conditions, we postulated that exposure to oxidant or antioxidant compounds could alter concentrations of NO in the exhaled breath (eNO). We assessed the effect of nitrogen dioxide (NO<sub>2</sub>) and ascorbic acid exposure on eNO in healthy human subjects. <h3>METHODS</h3> Ten healthy subjects were randomised to undergo a 20 minute single blind exposure to NO<sub>2</sub> (1.5 parts per million) or medical air in a crossover fashion. Exhaled NO and pulmonary function were measured before and for 3 hours after exposure. In a separate double blind crossover study 20 healthy subjects received ascorbic acid 500 mg twice daily or placebo for 2 weeks with a 6 week interim washout. Serum ascorbic acid levels and eNO were measured before and after each supplementation phase. <h3>RESULTS</h3> NO<sub>2</sub>induced a decrease of 0.62 (95% CI 0.32 to 0.92) ppb in the mean post-exposure eNO (p&lt;0.01) with no change in forced expiratory volume in 1 second (FEV<sub>1</sub>). Oral supplementation with ascorbic acid increased the mean serum ascorbic acid concentration by 7.4 (95% CI 5.1 to 9.7) μg/ml (63%) but did not alter eNO. <h3>CONCLUSIONS</h3> NO<sub>2</sub>exposure causes a decrease in eNO, an effect which may be mediated through changes in epithelial lining fluid redox state or through a direct effect on epithelial cells. In contrast, ascorbic acid does not appear to play a significant role in the metabolism of NO in the epithelial lining fluid.
818 VIRAL KINETICS AND PHARMACODYNAMICS OF ALBINTERFERON ALFA-2B IN INTERFERON TREATMENT-NAIVE PATIENTS WITH GENOTYPE 1, CHRONIC HEPATITIS C
Authors: A.U. Neumann, L. Rozenberg, V.G. Bain, J.G. McHutchison, E. Pulkstenis, G.M. Subramanian
Journal: Journal of Hepatology (2008)
Increased circulating soluble Fas in patients with dilated cardiomyopathy
Authors: Y. Shigematsu, H. Kawakami, T. Ohtsuka, H. Okayama, Y. Hayashi, Y. Hara, K. Kodama, M. Hamada, P. Qu, K. Hiwada
Journal: Journal of the American College of Cardiology (1998)
Obesity and Sex Steroids during Gonadotropin-Releasing Hormone Agonist Treatment for Prostate Cancer
Authors: Matthew R. Smith
Journal: Clinical Cancer Research (2007)

To evaluate effects of obesity on sex steroid levels during treatment with a gonadotropin-releasing hormone agonist in men with prostate cancer.Forty-nine hormone-naïve men with recurrent or locally advanced prostate cancer were included in the analyses. All subjects were treated with leuprolide 3-month depot for 48 weeks. Serum levels of estradiol, sex hormone-binding globulin, total testosterone, and free testosterone were assessed at baseline, 24 weeks, and 48 weeks. Subjects were categorized by body mass index (BMI) and percent body fat.Pretreatment serum sex hormone-binding globulin and total testosterone levels were significantly lower in overweight and obese men than in men with normal BMI. In the overall study population, mean serum testosterone concentrations decreased from 372 +/- 18 ng/dL at baseline to 13 +/- 1 ng/dL at week 48 (P < 0.001). Free testosterone decreased from 6.75 +/- 0.33 ng/dL at baseline to 0.21 +/- 0.02 ng/dL at week 48 (P < 0.001). During treatment with leuprolide, obese men had significantly higher total and free testosterone levels than men with normal BMI. Compared with normal men, total and free testosterone levels during treatment were 1.8-fold and 2.3-fold higher in obese men. Similar results were observed when subjects were categorized by body fat.Despite lower pretreatment serum testosterone levels, obese men have higher total and free testosterone levels during leuprolide treatment than men with normal BMI. These differences may contribute to the association between obesity and increased prostate cancer mortality.
Differences in the Effect of Individual Human Sera on Cell Cultures2
Authors: Erkki Saxén, Kari Penttinen
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Differences in the Effect of Individual Human Sera on Cell Cultures Get access Erkki Saxén, Erkki Saxén University of Helsinki, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar Kari Penttinen Kari Penttinen University of Helsinki, Finland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 35, Issue 1, July 1965, Pages 67–73, https://doi.org/10.1093/jnci/35.1.67 Published: 01 July 1965 Article history Received: 23 November 1964 Published: 01 July 1965
Herpes Simplex Virus Pneumonia
Authors: R. Gordon Douglas
Journal: JAMA (1969)

A 39-year-old white man with terminal panlobular emphysema underwent left lung allotransplantation. He was treated with azathioprine, steroids, antilymphocyte globulin, and antibiotics. The transplanted lung functioned well, but postoperatively oral ulcerations developed. The left lung became infiltrated and there was clinical deterioration. Herpes simplex virus was cultured from tracheal aspirates and lung biopsy material, and electron microscopic studies revealed intracellular herpesvirus-like particles. Treatment with cytarabine hydrochloride failed to result in clinical improvement and he died on the 26th day after operation.
A NOTE ON THE INCIDENCE OF RHEUMATIC HEART DISEASE AMONG CRIMINAL PSYCHOPATHS
Authors: WILLIAM R. ROSANOFF
Journal: American Journal of Psychiatry (1944)

Rheumatic heart lesions were present in 0.60 per cent of a group of 662 criminal psychopaths as compared to an incidence of 1.49 per cent in a roughly comparable control group of 18 and 19 year old selective service registrants. Rheumatic encephalopathy must be a very infrequent etiologic factor in the criminal types of psychopathic personality.
Cell-to-cell interaction prevents cell death in cultured neonatal rat ventricular myocytes
Authors: Kenji Yasui, Kenji Kada, Mayumi Hojo, Jong-Kook Lee, Kaichiro Kamiya, Junji Toyama, Tobias Opthof, Itsuo Kodama
Journal: Cardiovascular Research (2000)

Loss of cardiac cells and the anatomical or functional remodeling of intercellular coupling occur under several pathological conditions. We have assessed the significance of intercellular coupling for cell death.Ventricular cells obtained from 1 day old Wistar rats were cultured. Apoptosis was detected by nick-end labeling. Cells were plated at low and high cell density (3x10(4)/ml and 12x10(4)/ml, respectively). Cultured myocytes died spontaneously by apoptosis in a time dependent manner. The increase of the apoptotic cell population in a culture with high cell density on day 4 (1+/-1.2%, n=4) was significantly lower than that in a culture with low cell density (20+/-5.5%, n=4). The progression of apoptosis in the culture of low cell density was prevented in part after application of the medium extract from the culture of high cell density; the apoptotic cell population on day 6 decreased from 57+/-8.0% (n=4) to 36+/-3.8% (n=4). Treatment of the cultured myocytes at high cell density with antisense oligonucleotide for connexin43 (Cx43) for 24 h on day 2 resulted in a significant decrease in Cx43 expression as judged by Western blot, dye transfer and immunocytochemistry using mouse monoclonal antibody for Cx43. In association with the down-regulation of Cx43, the progress of apoptosis was accelerated; the apoptotic cell population on day 5 in the antisense-treated cultures (27+/-5.7%, n=4) was significantly higher than the sense-treated cultures (5+/-1.1%, n=4). The effect of Cx43 antisense treatment to promote apoptosis was not reversed by application of high cell-density culture medium.These findings suggest that cell-cell communication through gap junction formation and some humoral factors play important roles in the survival of cultured myocytes.
Intrinsic Resistance to JAK2 Inhibition in Myelofibrosis
Authors: Anna Kalota, Grace R. Jeschke, Martin Carroll, Elizabeth O. Hexner
Journal: Clinical Cancer Research (2013)

Recent results have shown that myeloproliferative neoplasms (MPN) are strongly associated with constitutive activation of the Janus-activated kinase (JAK)2 tyrosine kinase. However, JAK2 inhibitors currently approved or under development for treating myeloproliferative neoplasms do not selectively deplete the malignant clone, and the inhibition of activity of the drug target (JAK2) has not been rigorously evaluated in the clinical studies. Therefore, in this study we developed an in vitro assay to gain insight into how effectively JAK2 activity is inhibited in the samples of patients.We treated primary cells from normal donors and patients with MPN with JAK2 inhibitors and measured phosphorylation of downstream targets STAT5 and STAT3 by flow cytometry. Obtained results were next correlated with JAK2 V617F allele burden and plasma cytokine level.We observed a dose-dependent decrease in pSTAT5 and pSTAT3 in ex vivo treated granulocytes. However, phosphorylation of STAT3 and STAT5 in cells from patients with myelofibrosis was significantly less inhibited when compared with cells from patients with polycythemia vera, essential thrombocythemia, and normal donors. Sensitivity to inhibition did not correlate with JAK2 V617F clonal burden. Mixing studies using plasma from patients with myelofibrosis did not transfer resistance to sensitive cells. Likewise, no single cytokine measured seemed to account for the observed pattern of resistance.Taken together, these observations suggest that there are cell intrinsic mechanisms that define a priori resistance to JAK2 inhibition in myelofibrosis, and the lesion is localized upstream of STAT3 and STAT5.
Downloadable Algorithm to Reduce Inappropriate Shocks Caused by Fractures of Implantable Cardioverter-Defibrillator Leads
Authors: Charles D. Swerdlow, Bruce D. Gunderson, Kevin T. Ousdigian, Athula Abeyratne, Robert W. Stadler, Jeffrey M. Gillberg, Amisha S. Patel, Kenneth A. Ellenbogen
Journal: Circulation (2008)

Background— The primary method for monitoring implantable cardioverter-defibrillator lead integrity is periodic measurement of impedance. Sprint Fidelis leads are prone to pace-sense lead fractures, which commonly present as inappropriate shocks caused by oversensing. Methods and Results— We developed and tested an algorithm to enhance early identification of lead fractures and to reduce inappropriate shocks. This lead-integrity algorithm, which can be downloaded into presently implanted implantable cardioverter-defibrillators, alerts the patient and/or physician when triggered by either oversensing or excessive increases in impedance. To reduce inappropriate shocks, the lead-integrity algorithm increases the number of intervals to detect (NID) ventricular fibrillation when triggered. The lead-integrity algorithm was tested on data from 15 970 patients with Fidelis leads (including 121 with clinically diagnosed fractures) and 95 other fractured leads confirmed by analysis of returned product. The effect of the NID on inappropriate shocks was tested in 92 patients with 927 shocks caused by lead fracture. Increasing the NID reduced inappropriate shocks ( P &lt;0.0001). The lead-integrity algorithm provided at least a 3-day warning of inappropriate shocks in 76% (95% CI, 66 to 84) of patients versus 55% (95% CI, 43 to 64) for optimal impedance monitoring ( P =0.007). Its positive predictive value was 72% for lead fractures and 81% for lead fractures or header-connector problems requiring surgical intervention. The false-positive rate was 1 per 372 patient-years of monitoring. Conclusions— A lead-integrity algorithm developed for download into existing implantable cardioverter-defibrillators increases short-term warning of inappropriate shocks in patients with lead fractures and reduces the likelihood of inappropriate shocks. It is the first downloadable RAMware to enhance the performance of nominally functioning implantable cardioverter-defibrillators and the first implantable cardioverter-defibrillator monitoring feature that triggers real-time changes in ventricular fibrillation detection parameters to reduce inappropriate shocks.
Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn's disease
Authors: J Bauditz
Journal: Gut (2002)

Background: Thalidomide improves clinical symptoms in patients with therapy refractory Crohn's disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor α (TNF-α) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. Aim: The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). Methods: Ten patients with therapy refractory IBD (nine Crohn's disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-α, interleukin (IL)-1β, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. Results: Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-α and IL-12 decreased during treatment with thalidomide: LPMC (TNF-α: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-α: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1β and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-α and IL-12 production. Conclusion: The clinical effects of thalidomide in Crohn's disease may be mediated by reduction of both TNF-α and IL-12.
The Hypothermic Heart : Work Potential and Coronary Flow
Authors: I. K. R. McMillan, R. B. Case, W. N. Stainsby, G. H. Welch
Journal: Thorax (1957)

measured except for blood entering the right coronary artery.Pressures were measured in the left and right atria, and in the pulmonary artery and aortic arch by means of electromanometers, and, with the coronary flow and cardiac output, were continuously and simultan-
Injury in rugby league: a four year prospective survey.
Authors: S Stephenson, C Gissane, D Jennings
Journal: British Journal of Sports Medicine (1996)

To investigate the incidence of injury in English professional rugby league over a period of four playing seasons.All injuries that were received by players during match play were recorded. Each injury was classified according to site, type, player position, team playing for, activity at the time of injury, and time off as a result of injury.The overall injury rate was 114 (95% confidence interval 105 to 124) per 1000 playing hours, the most frequent type of injury were muscular injuries [34 (29 to 40) per 1000 playing hours], while the most frequently injured site was the head and neck region [38 (16 to 25) per 1000 playing hours]. Players received the largest percentage of injuries when being tackled [46.3% (41.9 to 50.7)], most injuries required less than one week away from playing and training [70.1% (66.1 to 74.2)], and forwards had a higher injury rate than backs (139 v 93 injuries per 1000 hours).The high rates of injury in rugby league are undoubtedly due to the high amount of bodily contact in the game. Being tackled has the highest risk of injury, because of being hit forcibly by other players. Forwards suffer higher injury rates than backs, probably because they are involved in a larger number of physical collisions.
Sensitive skin: an epidemiological study
Authors: C.M. Willis, S. Shaw, O. De Lacharriere, M. Baverel, L. Reiche, R. Jourdain, P. Bastien, J.D. Wilkinson
Journal: British Journal of Dermatology (2001)

There is a growing awareness that some individuals exhibit heightened skin sensitivity, particularly on the face, and have a high incidence of adverse reactions to cosmetics and toiletries.To carry out an epidemiological study to assess the prevalence of sensitive skin and cosmetic-related adverse events in a U.K. population, and to examine possible factors that may be associated with sensitive skin.Self-assessment questionnaires were sent out to 3300 women and 500 men, randomly selected, who were over the age of 18 years and lived within a 10-mile radius of High Wycombe (Bucks.). Fifty non-responder women were also questioned by telephone to ensure that the postal responders were representative of the population as a whole.The response rates were 62% for women and 52% for men, with the incidence of self-reported skin sensitivity being 51.4% and 38.2%, respectively. Ten per cent of women and 5.8% of men described themselves as having very sensitive skin. Fifty-seven per cent of women and 31.4% of men had experienced an adverse reaction to a personal product at some stage in their lives, with 23% of women and 13.8% of men having had a problem in the last 12 months. Among the women, symptoms of cosmetic-induced subjective sensory skin discomfort (burning, stinging, itching etc.) occurred more commonly in the sensitive skin cohort (53%) than in those who regarded themselves as non-sensitive (17%). An atopic diathesis in women did not appear to be a predictive factor for sensitive skin, the incidence of self-perceived sensitive skin being equivalent for atopics (49%) and non-atopics (51%). Furthermore, some 34% of atopic women described themselves as being non-sensitive. Nevertheless, the incidence of atopy was higher among the women in the sensitive skin group (49%) than among those in the non-sensitive group (27%). Dry skin and a predilection for blushing/flushing were associated factors for sensitive skin.Our survey indicates that sensitive facial skin is a common problem for women and men in the U.K. and points to the need for the development of personal products designed for this skin phenotype.
Regulation of proliferation and cytokine expression of bone marrow fibroblasts: role of c-myb.
Authors: C Szczylik, T Skorski, D H Ku, N C Nicolaides, S C Wen, L Rudnicka, A Bonati, L Malaguarnera, B Calabretta
Journal: The Journal of Experimental Medicine (1993)

The c-myb protooncogene plays a major role in regulating the process of in vitro and in vivo hematopoiesis via its activity as transcriptional regulator in hematopoietic progenitor cells. Since the bone marrow microenvironment appears to regulate in vivo hematopoiesis by maintaining the growth of multipotent progenitors via secretion of specific cytokines, we asked whether c-myb is also required for the proliferation of and/or cytokine production by stromal cells that generate fibroblast-like colonies (fibroblast colony-forming units [CFU-F]). Using the reverse transcriptase polymerase chain reaction technique, we detected low levels of c-myb mRNA transcripts in human normal bone marrow fibroblasts. Treatment of these cells with c-myb antisense oligodeoxynucleotides caused downregulation of c-myb expression, decreased in the number of marrow CFU-F colonies (approximately 54% inhibition) and in the cell number within residual colonies (approximately 80%), and downregulation of granulocyte/macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF) mRNA expression. Transfection of T98G glioblastoma cells, in which expression of c-myb, GM-CSF, and SCF mRNAs is undetectable or barely detectable, with a plasmid containing a full-length c-myb cDNA under the control of the SV40 promoter induced the expression of biologically active SCF and GM-CSF in these cells. Regulation of GM-CSF expression by c-myb was due in part to transactivation of the GM-CSF promoter. These results indicate that, in addition to regulating hematopoietic cell proliferation, c-myb is also required for proliferation of and cytokines synthesis by bone marrow fibroblasts.