tbuckley/cabot-search huggingface dataset:
Fueling CD4+ T cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Deconstructing I B kinaseOn page 1677, Ruocco et al. show that the formation of bone-resorbing osteoclasts is crippled when the ␤ subunit of the NF-B-activating I B kinase (IKK) complex is missing.The absence of IKK ␤ also protected mice against inflammatoryinduced bone loss, a complication of inflammatory diseases such as rheumatoid arthritis (RA) that is caused by excessive activation of osteoclasts.The osteoclast growth factor RANKL (receptor activator of NF-B ligand) activates the transcription factor NF-B, which promotes osteoclast development.NF-B activation requires the upstream IKK complex (IKK ␣ , ␤ , ␥ ), which releases NF-B from its inhibitor protein.Although a recent report showed that the IKK complex is required for osteoclast development, the relative importance of the two catalytic subunits of IKK ( ␣ , ␤ ) in this process remained unclear.Ruocco et al. now show that mice lacking IKK ␤ were unable to generate osteoclasts and developed severe osteopetrosis (increased bone formation), whereas those lacking IKK ␣ activity had no apparent bone abnormalities.The IKK ␤ -deficient mice failed to transmit RANKL signals and had increased TNF-induced apoptosis in osteoclast precursors.Osteoclast formation was partially restored in mice that lacked both IKK ␤ and the type I TNF receptor.IKK ␤ -deficient mice were also resistant to inflammatory bone loss and this resistance was dependent on TNF-derived signals.Thus the authors suggest that drugs designed to block IKK ␤ may prevent bone loss in patients.However, they caution that such drugs, if developed, should perhaps not be combined with anti-TNF therapy (commonly used to treat RA) as the combination may not be effective.
Idiopathic ventricular fibrillation: inducibility and beneficial effects of class I antiarrhythmic agents.
Authors: B Belhassen, I Shapira, D Shoshani, A Paredes, H Miller, S Laniado
Journal: Circulation (1987)

Ventricular fibrillation in patients without recognizable heart disease is uncommon and electrophysiologic data on such patients is limited. Over a 7 year period, five patients (three men and two women, ranging in age from 24 to 52 years) without demonstrable heart disease underwent electrophysiologic studies with pharmacologic drug testing because of single (four patients) or multiple (one patient) documented episodes of ventricular fibrillation. The arrhythmic event was unrelated to myocardial ischemia or infarction, metabolic or electrolyte disturbances, drug toxicity, preexcitation, or prolonged QT syndromes. In all three patients receiving no antiarrhythmic drugs and in two pretreated with amiodarone, a rapid poorly tolerated ventricular tachyarrhythmia requiring cardioversion was induced by programmed ventricular stimulation with up to two extrastimuli. In all instances, addition of either oral quinidine or oral disopyramide prevented the induction of sustained ventricular arrhythmias. All five patients were placed on antiarrhythmic drug regimens found effective during electrophysiologic studies and remained asymptomatic during follow-up periods ranging from 12 to 93 (mean 52) months. We conclude that in the patients with idiopathic ventricular fibrillation in our study: programmed ventricular stimulation reliably replicated the spontaneous arrhythmia, class I antiarrhythmic agents effectively prevented induction of the arrhythmia in the laboratory, and in contrast to the severity of the presenting arrhythmia, a benign clinical course was observed during long-term therapy with class I antiarrhythmic agents.
Eosinophilic myenteric ganglionitis is associated with functional intestinal obstruction
Authors: M G Schappi
Journal: Gut (2003)

The diagnostic features and clinical course of three children (aged 1 month to 15 years) with severe functional intestinal obstruction and inflammation of the colonic lamina propria and myenteric plexus are described. The myenteric inflammatory infiltrate was eosinophil predominant with none of the immunological characteristics of lymphocytic ganglionitis. Neurones in the myenteric ganglia expressed the potent eosinophil chemoattractant interleukin 5. None responded to dietary exclusion but all three responded symptomatically to immunosuppression/anti-inflammatory treatments. Eosinophilic ganglionitis is associated with a pseudo-obstructive syndrome which is amenable to anti-inflammatory treatment.
Case of Rectal GI Stromal Tumor Demonstrating that <i>KIT</i> and <i>PDGFRA</i> Mutations Are Not Always Mutually Exclusive
Authors: Riccardo Ricci, Maurizio Martini, Tonia Cenci, Armando Antinori, Alessandra Cassano, Luigi M. Larocca
Journal: Journal of Clinical Oncology (2014)
Quantitative cerebrospinal fluid acid-base balance in acute respiratory alkalosis.
Authors: S Javaheri, W Corbett, K Wagner, J M Adams
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Data on canine cisternal cerebrospinal fluid (CSF) ions in acute respiratory alkalosis are limited and fragmentary. We hypothesized that with the fall in arterial PCO2 (PaCO2) and in the face of normal osmoregulation, CSF [Na+] remains relatively constant and CSF [Na+-Cl-] narrows to account in part for the fall in CSF [HCO3-]. We therefore measured blood and CSF acid-base variables and ions of two groups of pentobarbital-anesthetized, mechanically ventilated dogs (n = 10 in each group). In the control group, PaCO2 was kept constant and changes in serum and CSF ions were minimal. In Group II (acute respiratory alkalosis), both PaCO2 and cisternal CSF PCO2 decreased by 10 mm Hg. Five hours after induction of respiratory alkalosis, mean CSF [HCO3-] decreased significantly by 4.4 +/- 1.2 mEq/L (mean +/- SD). The fall in CSF [HCO3-] was similar to changes in CSF strong ion difference (SID = Na(+)+K(+)+Ca(2+)+Mg(2+)-CL(-)-lactate), which decreased 4.4 +/- 1.9 mEq/L. Concentrations of the four major CSF cations did not change significantly. Cisternal CSF lactate rose significantly by 1.2 +/- 0.9 mEq/L, accounting for 25% of the change in CSF [HCO3-]. The remaining (75%) change in CSF [HCO3-] was accounted for by changes in CSF [Cl-].
The Cyclin-dependent Kinase Inhibitor CYC202 (<b> <i>R</i> </b>-Roscovitine) Inhibits Retinoblastoma Protein Phosphorylation, Causes Loss of Cyclin D1, and Activates the Mitogen-activated Protein Kinase Pathway
Authors: Steven R. Whittaker, Mike I. Walton, Michelle D. Garrett, Paul Workman
Journal: Cancer Research (2004)

Abstract Deregulation of the cell cycle commonly occurs during tumorigenesis, resulting in unrestricted cell proliferation and independence from mitogens. Cyclin-dependent kinase inhibitors have the potential to induce cell cycle arrest and apoptosis in cancer cells. CYC202 (R-roscovitine) is a potent inhibitor of CDK2/cyclin E that is undergoing clinical trials. Drugs selected to act on a particular molecular target may exert additional or alternative effects in intact cells. We therefore studied the molecular pharmacology of CYC202 in human colon cancer cells. Treatment of HT29 and KM12 colon carcinoma cell lines with CYC202 decreased both retinoblastoma protein phosphorylation and total retinoblastoma protein. In addition, an increase in the phosphorylation of extracellular signal-regulated kinases 1/2 was observed. As a result, downstream activation of the mitogen-activated protein kinase pathway occurred, as demonstrated by an increase in ELK-1 phosphorylation and in c-FOS expression. Use of mitogen-activated protein kinase kinases 1/2 inhibitors showed that the CYC202-induced extracellular signal-regulated kinases 1/2 phosphorylation was mitogen-activated protein kinase kinases 1/2 dependent but did not contribute to the cell cycle effects of the drug, which included a reduction of cells in G1, inhibition of bromodeoxyuridine incorporation during S-phase, and a moderate increase in G2-M phase. Despite activation of the mitogen-activated protein kinase pathway, cyclin D1 protein levels were decreased by CYC202, an effect that occurred simultaneously with loss of retinoblastoma protein phosphorylation and inhibition of cell cycle progression. The reduced expression of cyclin D1 protein was independent of the p38SAPK and phosphatidylinositol 3-kinase pathways, which are known regulators of cyclin D1 protein. Interestingly, CYC202 caused a clear reduction in cyclins D1, A, and B1 mRNA, whereas c-FOS mRNA increased by 2-fold. This was accompanied by a loss of RNA polymerase II phosphorylation and total RNA polymerase II protein, suggesting that CYC202 was inhibiting transcription, possibly via inhibition of CDK7 and CDK9 complexes. It can be concluded that although CYC202 can act as a CDK2 inhibitor, it also has the potential to inhibit CDK4 and CDK1 activities in cancer cells through the down-regulation of the corresponding cyclin partners. This provides a possible mechanism by which CYC202 can cause a reduction in retinoblastoma protein phosphorylation at multiple sites and cell cycle arrest in G1, S, and G2-M phases. In addition to providing useful insights into the molecular pharmacology of CYC202 in human cancer cells, the results also suggest potential pharmacodynamic end points for use in clinical trials with the drug.
Drug Use and Life Style Among College Undergraduates: A 30-Year Longitudinal Study
Authors: H G Pope, M Ionescu-Pioggia, K W Pope
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors examined trends in the prevalence of substance use and its relationship to attributes of life style among college students over a 30-year period. METHOD: They distributed anonymous questionnaires to 796 seniors at a large New England college in 1999, using methods essentially identical to those of their previous studies at the same college in 1969, 1978, and 1989. RESULTS: Most forms of drug use rose to a peak in 1978 then fell over the next 21 years, except for use of 3,4-methylenedioxymethamphetamine (“ecstasy”). On several variables, college substance users differed more sharply from nonusers in 1999 than in previous decades. CONCLUSIONS: Although the study was limited to students at a single institution, its findings suggest that college drug use is generally declining and that users have increasingly diverged from nonusers in their values and life style.
Thalidomide in actinic prurigo
Authors: C.R. LOVELL, J.L.M. HAWK, C.D. CALNAN, I.A. MAGNUS
Journal: British Journal of Dermatology (1983)

Journal Article Thalidomide in actinic prurigo Get access C.R. LOVELL, C.R. LOVELL St John's Hospital for Diseases of the Skin, 5 Lisle Street, London wc2h 7bj, England Search for other works by this author on: Oxford Academic Google Scholar J.L.M. HAWK, J.L.M. HAWK St John's Hospital for Diseases of the Skin, 5 Lisle Street, London wc2h 7bj, England Search for other works by this author on: Oxford Academic Google Scholar C.D. CALNAN, C.D. CALNAN St John's Hospital for Diseases of the Skin, 5 Lisle Street, London wc2h 7bj, England Search for other works by this author on: Oxford Academic Google Scholar I.A. MAGNUS I.A. MAGNUS St John's Hospital for Diseases of the Skin, 5 Lisle Street, London wc2h 7bj, England Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 4, 1 April 1983, Pages 467–471, https://doi.org/10.1111/j.1365-2133.1983.tb04601.x Published: 01 April 1983 Article history Accepted: 07 September 1982 Published: 01 April 1983
Plasma Catecholamines and Carbohydrate Metabolism in Patients with Acute Myocardial Infarction
Authors: Niels Juel Christensen, Jørgen Videbaek
Journal: Journal of Clinical Investigation (1974)

Blood glucose, glucose tolerance, serum insulin, free fatty acids in serum, plasma noradrenaline, and plasma adrenaline were measured in 10 patients with acute myocardial infarction (AMI) as well as in healthy subjects. Both noradrenaline and adrenaline in plasma were elevated in patients with AMI, the level being fairly constant in the individual patients and dependent on their degree of illness. In the fasting state, blood glucose, serum insulin, and free fatty acids were elevated in patients with AMI. Plasma noradrenaline showed a highly significant correlation with the fasting blood glucose concentration, but not with serum insulin or free fatty acids. The concentration of free fatty acids in serum could be predicted only if both plasma noradrenaline and the basal insulin concentration were known. Intravenous glucose tolerance was reduced in patients with AMI, especially in patients with high plasma noradrenaline and a low initial rise in insulin. There was a significant negative correlation between the initial rise in insulin expressed in percentage of the basal insulin concentration and the plasma noradrenaline level. The statistical effects of serum insulin and plasma noradrenaline on the glucose tolerance could not be separated from each other. The decline in free fatty acids after intravenous injection of glucose showed a negative correlation with plasma noradrenaline and a positive correlation with the initial rise in insulin. Plasma adrenaline did not correlate with any of the metabolic parameters mentioned above. The plasma noradrenaline concentration was elevated to such a degree in patients with AMI that the observed changes in metabolism might have been caused directly by the circulating noradrenaline. During the glucose tolerance tests, the effects of noradrenaline was probably carried out indirectly via a suppression of insulin secretion. It is conceivable that any effect of plasma noradrenaline on the basal insulin secretion was neutralized by the fasting hyperglycemia.
Case-Control Study on Histologically Determined Multiple Primary Lung Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: H Sugimura, S Watanabe, S Tsugane, S Morinaga, T Yoneyama
Journal: JNCI Journal of the National Cancer Institute (1987)

Between 1965 and 1985, 72 (64 male and 8 female) cases of multiple primary lung cancer (MPLC) in the National Cancer Center Hospital, Japan, were reviewed, and a retrospective hospital-based case-control study was performed with special reference to the patients' smoking and family histories. Control cases were selected from patients with unicentric lung cancer (ULC) with a longer survival time than that for other patients with whom they were matched for age, sex, histologic examination of primary lung cancer, and residence in prefecture. The overall percentage of MPLC was higher in males (3.1%) than in females (1.8%). Of the total number of cases, 46 were synchronous and 26, metachronous. The same histology was recognized in 38 cases (53%), and squamous cell carcinomas were observed in 65% of MPLC cases, all of whom were smokers. At least half of the MPLC found in non-smokers were adenocarcinomas. Habitual smokers, with a Brinkman index (BI) of more than 50, accounted for 90% of all cases of MPLC, although 81% of the controls were also habitual smokers. A positive relationship dependent on the number of cigarettes smoked was observed between the Bl of smokers and the proportion suffering MPLC. There was a family history of cancer in 47% of MPLC cases while, for controls, this figure was 40%. It was found that 67% of patients with MPLC and 61% with ULC were drinkers. The influence of cigarette smoking on MPLC was confirmed, especially in the cases of squamous cell carcinoma and small-cell carcinoma.
Steroid injection for inferior heel pain: a randomised controlled trial
Authors: Elisabeth M A Ball, Helen M A McKeeman, Christopher Patterson, James Burns, Wing Hoi Yau, Owen A Moore, Claire Benson, Joanne Foo, Gary D Wright, Allister J Taggart
Journal: Annals of the Rheumatic Diseases (2012)

Plantar fasciitis is a common cause of heel pain. The aim of this study was twofold: to compare steroid injection with placebo injection and to compare ultrasound guided with unguided steroid injection in the management of this condition.65 patients with inferior heel pain were recruited between November 2008 and June 2011. Heel pain was measured using a visual analogue scale (VAS) at baseline and follow-up 6 and 12 weeks after injection.22 patients were randomised to ultrasound guided steroid injection, 21 patients to palpation guided steroid injection and 22 to ultrasound guided placebo injection. There was a significant difference in VAS scores between the groups at 6 and 12 weeks (p=0.018 and p=0.004, respectively). There was a 19.7 (95% CI 2.5 to 37.0) difference in mean VAS scores at 6 weeks between the ultrasound guided steroid group and the placebo group and a 24.0 (95% CI 6.6 to 41.3) difference between the unguided steroid group and the placebo group at 6 weeks. At 12 weeks, the mean difference was 25.1 (95% CI 6.5 to 43.6) and 28.4 (95% CI 11.1 to 45.7) respectively between both steroid injection groups and the placebo group. There was no difference in VAS scores following steroid injection between the ultrasound guided and the unguided groups at either time point. Plantar fascia thickness was significantly reduced after injection in both active treatment groups (p=0.00).In this study, steroid injection showed a clear benefit over placebo at 6 weeks and this difference was maintained at 12 weeks. Trial Registration No ISRCTN79628180 (www.controlled-trials.com).
Long-Term Reactions to Genetic Testing for<i>BRCA1</i>and<i>BRCA2</i>Mutations: Does Time Heal Women's Concerns?
Authors: Chanita Hughes Halbert, Jill E. Stopfer, Jasmine McDonald, Benita Weathers, Aliya Collier, Andrea B. Troxel, Susan Domchek
Journal: Journal of Clinical Oncology (2011)

Purpose Short-term reactions to BRCA1 and BRCA2 (BRCA1/2) genetic test results have been described in several reports, but the long-terms effects of testing have not been examined extensively. Methods We conducted an observational study to characterize the long-term impact of genetic testing for BRCA1/2 mutations in 167 women who had received genetic test results at least 4 years ago. We also evaluated the relationship between genetic testing–specific reactions and breast and ovarian cancer screening to determine the behavioral significance of adverse reactions. Results Seventy-four percent of women were not experiencing any distress regarding their test result, 41% were not experiencing any uncertainty, and 51% had a score for positive experiences that was suggestive of low levels of adverse reactions in terms of family support and communication. Mutation carriers (odds ratio, 3.96; 95% CI, 1.44 to 10.89; P = .01) were most likely to experience distress. Only less time since disclosure was related significantly to experiencing uncertainty (odds ratio, 0.62; 95% CI, 0.44 to 0.88; P = .008). In terms of cancer screening, 81% of women had a mammogram during the year before study enrollment, 25% had magnetic resonance imaging (MRI), 20% had a transvaginal ultrasound, and 20% had a CA-125. Experiencing distress was associated significantly with having a CA-125 (χ 2 = 3.89, P = .05), and uncertainty was associated with having an MRI (χ 2 = 8.90, P = .003). Conclusion Our findings show that women are not likely to experience genetic testing concerns several years after receiving BRCA1/2 test results; distress and uncertainty are not likely to have adverse effects on screening among women at risk for hereditary disease.
A fifth of acute trusts may be under-reporting medical errors
Authors: Z. Kmietowicz
Journal: BMJ (2014)

England’s health secretary, Jeremy Hunt, has said that hospitals must do more to improve their reporting and responses concerning safety incidents, after a review found that a fifth of acute NHS trusts in England were not reporting the expected number of safety incidents.

He said that hospital trusts are to be given financial incentives if they produce safety plans that would cut litigation costs by reducing the number of avoidable incidents that occurred on their premises.

Data from the Department of Health showed that 25 of 141 trusts in England (18%) were classed as good in terms of their commitment to be open and honest about mistakes, 87 (62%) were rated as satisfactory, and 29 (21%) were given a red rating, indicating a poor performance. A poor rating meant that hospitals were reporting too few safety incidents or were not reporting often enough or that staff thought that their trust was not responding adequately …
Is an interactive voice response system (IVRS) effective in contributing to avoiding unplanned admissions in chronic obstructive pulmonary disease (COPD) patients
Authors: Joanne King, Richard Russell
Journal: European Respiratory Journal (2013)

Introduction

Many community services have been implemented over the past five years to support patients with COPD at home when exacerbating, including the use of telemonitoring. The evaluation of these new technologies is limited, variable and controversial (Wootton 2012, Journal of Telemedicine and Telecare 18: (4) 211-220).

Aim

To evaluate an IVRS used within a local service providing early discharge and admission avoidance to patients with COPD. To assess the effect of telehealth delivered in this way on admission rates of this group of patients.

Method

A service evaluation was conducted examining retrospective data comparing the admission rates of patients who had access to the IVRS and usual care (n =20) and those who had access to usual care alone (n =20). Demographic data and admission frequency 12 months before and after the instigation of the IVRS and twelve months before and after engagement with the team without IVRS were examined.

Results

Data is presented as mean +- SEM. Data analysed using Mann Whitney u test. When comparing the admission history of the group receiving IVRS and those receiving usual care alone there was a significant reduction in admissions within the telehealth group (-0.3 +0.28 v 0.7 +0.35 p= 0.0287). Telehealth appeared to provide a positive influence on the number of admissions that the group experienced after its introduction although within the IVRS group alone this did not achieve statistical significance (p = 0.336).

Conclusion

Whilst it appears that the use of the IVR in patients with COPD assists in reducing admission rates, further evaluation is needed to be confident of its effects.
Inferring Divergence of Context-Dependent Substitution Rates in Drosophila Genomes with Applications to Comparative Genomics
Authors: R. Chachick, A. Tanay
Journal: Molecular Biology and Evolution (2012)

Nucleotide substitution is a major evolutionary driving force that can incrementally and stochastically give rise to broad divergence patterns among species. The substitution process at each genomic position is frequently modeled independently of the other positions, although complex interactions between nearby bases are known to significantly affect mutation rates. Here, we study the evolution of 12 fly genomes using new algorithms for accurate inference of parameter-rich substitution models. By comparing models between lineages, we reveal the evolutionary histories of substitution rates at different flanking nucleotide contexts. We demonstrate these driving forces of molecular evolution to be constantly changing, suggesting that neutral drift of mutation rates is an important factor in the evolution of genomes and their sequence composition. This observation is used to develop a scalable approach for parameter-rich comparative genomics. By screening short DNA sequences, we demonstrate how homeoboxes and other transcription factor binding motifs are highly conserved based on our parameter-rich models but not according to standard conservation assays. With the increasing availability of genome sequences, rich substitution models become an attractive and practical approach for evolutionary analysis in general and comparative genomics in particular.