tbuckley/cabot-search huggingface dataset:
Direct regulation by calcium of cytoplasmic messenger ribonucleic acid coding for pre-proparathyroid hormone in isolated bovine parathyroid cells.
Authors: J Russell, D Lettieri, L M Sherwood
Journal: Journal of Clinical Investigation (1983)

DNA complementary to bovine preproparathyroid hormone mRNA was cloned and labeled by nick translation in order to measure mRNA by molecular hybridization. Bovine parathyroid cells were maintained in primary tissue culture for periods up to 96 h at 0.5 mM, 1.25 mM, and 2.5 mM calcium, which was followed by extraction of cellular RNA. Levels of mRNA showed no differences at 0.5 or 1.25 mM calcium, but at high calcium levels, there was a reversible decrease that began at 16 h to a plateau at 30% of control after 72 h. These studies suggest that the glandular capacity to synthesize hormone may be at or near maximal at normal calcium, but at high calcium, there is a decrease over time in steady state levels of mRNA.
Allergen-responsive CD4+CD25+ Regulatory T Cells in Children who Have Outgrown Cow's Milk Allergy
Authors: Malin R. Karlsson, Jarle Rugtveit, Per Brandtzaeg
Journal: The Journal of Experimental Medicine (2004)

Cow's milk allergy in children is often of short duration, which makes this disorder an interesting clinical model for studies of tolerance to dietary antigens. Here, we studied T cell responses in 21 initially allergic children who, after a milk-free period of >2 mo, had cow's milk reintroduced to their diet. Children who outgrew their allergy (tolerant children) had higher frequencies of circulating CD4(+)CD25(+) T cells and decreased in vitro proliferative responses to bovine beta-lactoglobulin in peripheral blood mononuclear cells (PBMCs) compared with children who maintained clinically active allergy. No significant difference in proliferative activity stimulated by the polyclonal mitogen phytohemagglutinin was observed between the two groups. Depletion of CD25(+) cells from PBMCs of tolerant children led to a fivefold increase in in vitro proliferation against beta-lactoglobulin. This suggests that tolerance is associated with the appearance of circulating CD4(+)CD25(+) regulatory T (Treg) cells that are capable of suppressing the effector T cells generated 1 wk after reintroduction of cow's milk. The suppressive function of the CD4(+)CD25(+) Treg cells was shown to be partly cell contact dependent. Collectively, our study provides human data to suggest that mucosal induction of tolerance against dietary antigens is associated with the development of CD4(+)CD25(+) Treg cells.
Role of glycogen synthase kinase 3 beta (GSK3beta) in mediating the cytotoxic effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast cancer cells.
Authors: John P Alao, Alexandra V Stavropoulou, Eric Lam, R Charles Coombes
Journal: Molecular Cancer (2006)

Histone deacetylase inhibitors (HDACIs) have been shown to induce apoptotic and autophagic cell death in vitro and in vivo. The molecular mechanisms that underlie these cytotoxic effects are not yet clearly understood. Recently, HDACIs were shown to induce Akt dephosphorylation by disrupting HDAC-protein phosphatase 1 (PP1) complexes. This disruption results in the increased association of PP1 with Akt, resulting in the dephosphorylation and consequent inactivation of the kinase. Akt enhances cellular survival through the phosphorylation-dependent inhibition of several pro-apoptotic proteins. Akt is an important negative regulator of GSK3β, a kinase that has been shown to regulate apoptosis in response to various stimuli. In the present study, we investigated the role of GSK3β in mediating the cytotoxic effects in MCF-7 breast cancer cells treated with trichostatin A (TSA), a prototype HDACI. We show that TSA induces Akt dephosphorylation in a PP1-dependent manner, resulting in activation of GSK3β in MCF-7 cells. Similarly, knockdown of HDAC1 and-2 by small interfering RNA (siRNA) resulted in the dephosphorylation of Akt and GSK3β. Selective inhibition of GSK3β attenuated TSA induced cytotoxicity and resulted in enhanced proliferation following drug removal. Our findings identify GSK3β as an important mediator of TSA-induced cytotoxicity in MCF-7 breast cancer cells.
A Lecture ON OXYGEN WANT AND THE MEANS OF ITS RELIEF
Authors: A. G. Auld
Journal: BMJ (1914)

MAY i6, !9r4 gliddiness might be so pronounce(d asto compel him to stop work anid to go home in a cab.Rest led to disappearance of these svfliptonis.Thle pulse wvas 60, anid the arterial pressure was 110 mm.On lyhing down the pulse was definitely fuller thall wl eni sittillg.Tlhe vessels were soft.The heart at the apex was in the mi-ammary line; the sounds were fairly good and closed.The abdomeil presented nio abniormality; to regulate the bowels apeiita was takein regsularlyv.The urine presented no abnormal characters.In this patient the lieadache and giddiness were pri- miiarily cerebral, and were to be regarded ass tlhe result of disordered cerebral circulation, due to too close mental application, or to emotional influences.Tllere could be no doubt that there was an imperative call for complete mental rest, away from the patient's ordinary environ- inent.Here, again, on the hiypothesis of local cerebral aingioplaslmi being the cause of the phenomenia, tlle danger was lnot that in onle of these attacks oerebral hiaemorrhage wvould occur, butt that the angiospasm miglht be so pro- nounced and of sufficient duration to lead to cerebral softeninig in the inore purely miental areas of the brain.
Serum Mannan-Binding Lectin-Associated Serine Protease 2 Levels in Colorectal Cancer: Relation to Recurrence and Mortality
Authors: Henriette Ytting, Ib Jarle Christensen, Steffen Thiel, Jens Christian Jensenius, Hans Jørgen Nielsen
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Mannan-binding lectin-associated serine protease 2 (MASP-2) is a plasma protein involved in inflammatory processes. MASP-2 circulates in complex with the protein mannan-binding lectin (MBL) or ficolins, and is activated to recruit the complement system when MBL binds to its targets. The level of MASP-2 is genetically determined, and the aim of the present study was to evaluate the effect of MASP-2 levels on postoperative infection, recurrence and survival. Experimental Design: MASP-2 concentrations were determined in serum from 605 patients collected before elective resection for primary colorectal cancer. The primary end points were postoperative infection, time to any recurrence, and time to death. The median time of follow-up was 7.9 years. Results: MASP-2 levels were not correlated to postoperative infections (P = 0.49). High MASP-2 levels significantly correlated with recurrent cancer disease [P = 0.03; hazard ratio (HR) = 1.4; 95% confidence interval (CI), 1.0-2.0] and with poor survival (P = 0.0005; HR = 1.4; 95% CI, 1.2-1.7). Multivariate statistical analysis, including age, gender, Dukes' stage of disease, tumor localization, and postoperative pneumonia, showed that the MASP-2 level had an independent prognostic value in the patients (P = 0.0001; HR = 1.5; 95% CI, 1.2-1.8). Conclusion: In the cohort of patients with colorectal cancer investigated, MASP-2 concentration in serum proved to be an independent prognostic marker with high MASP-2 levels predicting recurrence and poor survival. Postoperative infection could not be shown to be associated with MASP-2 levels.
New-generation vaccines against cholera
Authors: John Clemens, Sunheang Shin, Dipika Sur, G. Balakrish Nair, Jan Holmgren
Journal: Nature Reviews Gastroenterology & Hepatology (2011)

Currently, vaccines are not widely used in the control of cholera, but new-generation orally administered vaccines may well become important tools in the public health armamentarium against this disease. This Review focuses on selected aspects of the disease, its pathogenesis and immunology, clinical features, epidemiology and treatment, and summarizes the status of new-generation cholera vaccines. Cholera is a major global health problem, causing approximately 100,000 deaths annually, about half of which occur in sub-Saharan Africa. Although early-generation parenteral cholera vaccines were abandoned as public health tools owing to their limited efficacy, newer-generation oral cholera vaccines have attractive safety and protection profiles. Both killed and live oral vaccines have been licensed, although only killed oral vaccines are currently manufactured and available. These killed oral vaccines not only provide direct protection to vaccinated individuals, but also confer herd immunity. The combination of direct vaccine protection and vaccine herd immunity effects makes these vaccines highly cost-effective and, therefore, attractive for use in developing countries. Administration of these oral vaccines does not require qualified medical personnel, which makes their use practical—even in developing countries. Although new-generation oral cholera vaccines should not be considered in isolation from other preventive approaches, especially improved water quality and sanitation, they represent important tools in the public health armamentarium to control both endemic and epidemic cholera.
The Effects of Psychosocial Services in Substance Abuse Treatment
Authors: A T McLellan, I O Arndt, D S Metzger, G E Woody, C P O'Brien
Journal: JAMA (1993)

To examine whether the addition of counseling, medical care, and psychosocial services improves the efficacy of methadone hydrochloride therapy in the rehabilitation of opiate-dependent patients.Random assignment to one of three treatment groups for a 6-month clinical trial: (1) minimum methadone services (MMS)--methadone alone (a minimum of 60 mg/d) with no other services; (2) standard methadone services (SMS)--same dose of methadone plus counseling; or (3) enhanced methadone services (EMS)--same dose of methadone plus counseling and on-site medical/psychiatric, employment, and family therapy.The methadone maintenance program of the Philadelphia (Pa) Veterans Affairs Medical Center.Ninety-two male intravenous opiate users in methadone maintenance treatment.While methadone treatment alone (MMS) was associated with reductions in opiate use, 69% of these subjects had to be "protectively transferred" from the trial because of unremitting use of opiates or cocaine, or medical/psychiatric emergencies. This was significantly different from the 41% of SMS subjects and 19% of EMS subjects who met the criteria. End-of-treatment data (at 24 weeks) showed minimal improvements among the 10 MMS patients who completed the trial. The SMS group showed significantly more and larger improvements than did the MMS group; and the EMS group showed significantly better outcomes than did the SMS group. Minimum methadone services subjects who had been "protectively transferred" to standard care showed significant reductions in opiate and cocaine use within 4 weeks.Methadone alone (even in substantial doses) may only be effective for a minority of eligible patients. The addition of basic counseling was associated with major increases in efficacy; and the addition of on-site professional services was even more effective.
Pretest Prediction of BRCA1 or BRCA2 Mutation by Risk Counselors and the Computer Model BRCAPRO
Authors: David M. Euhus, Kristin C. Smith, Linda Robinson, Amy Stucky, Olufunmilayo I. Olopade, Shelly Cummings, Judy E. Garber, Anu Chittenden, Gordon B. Mills, Paula Rieger, Laura Esserman, Beth Crawford, Kevin S. Hughes, Connie A. Roche, Patricia A. Ganz, Joyce Seldon, Carol J. Fabian, Jennifer Klemp, Gail Tomlinson
Journal: JNCI Journal of the National Cancer Institute (2002)

Because BRCA gene mutation testing is costly, occasionally uninformative, and frequently associated with ethical and legal issues, careful patient selection is required prior to testing. Estimation of BRCA gene mutation probability is an important component of pretest counseling, but the accuracy of these estimates is currently unknown. We measured the performance of eight cancer risk counselors and of a computer model, BRCAPRO, at identifying families likely to carry a BRCA gene mutation.Eight cancer risk counselors and the computer model BRCAPRO estimated BRCA gene mutation probabilities for 148 pedigrees selected from an initial sample of 272 pedigrees. The final sample was limited to pedigrees with a proband affected by breast or ovarian cancer and BRCA1 and BRCA2 gene sequencing results unequivocally reported as negative or positive for a deleterious mutation. Sensitivity, specificity, negative predictive value, positive predictive value, and areas under receiver operator characteristics (ROC) curves were calculated for each risk counselor and for BRCAPRO. All statistical tests were two sided.Using a greater-than-10% BRCA gene mutation probability threshold, the median sensitivity for identifying mutation carriers was 94% (range = 81% to 98%) for the eight risk counselors and 92% (range = 91% to 92%) for BRCAPRO. Median specificity at this threshold was 16% (range = 6% to 34%) for the risk counselors and 32% (range = 30% to 34%) for BRCAPRO (P =.04). Median area under the ROC curves was 0.671 for the risk counselors (range = 0.620 to 0.717) and 0.712 (range = 0.706 to 0.720) for BRCAPRO (P =.04). There was a slight, but not statistically significant, improvement in all counselor performance measures when BRCAPRO-assigned gene mutation probability information was included with the pedigrees.Sensitivity for identifying BRCA gene mutation carriers is similar for experienced risk counselors and the computer model BRCAPRO. Because the computer model consistently demonstrated superior specificity, overall discrimination between BRCA gene mutation carriers and BRCA gene mutation noncarriers was slightly better for BRCAPRO.
Early-Onset Pauciarticular Juvenile Rheumatoid Arthritis Associated with Human Leukocyte Antigen-DRw5, Iritis, and Antinuclear Antibody
Authors: D. Glass, D. Litvin, K. Wallace, L. Chylack, M. Garovoy, C. B. Carpenter, P. H. Schur
Journal: Journal of Clinical Investigation (1980)

Evidence has been sought for a genetically determined predisposition among children with juvenile rheumatoid arthritis (JRA) who are also at particular risk for the development of inflammatory eye disease.
Energy Balance, Polymorphisms in the mTOR Pathway, and Renal Cell Carcinoma Risk
Authors: Xiang Shu, Jie Lin, Christopher G. Wood, Nizar M. Tannir, Xifeng Wu
Journal: JNCI Journal of the National Cancer Institute (2013)

The interplay between obesity, physical activity, weight gain, and genetic variants in the mTOR pathway has not been studied in renal cell carcinoma (RCC). We examined the associations between obesity, weight gain, physical activity, and RCC risk. We also analyzed whether genetic variants in the mTOR pathway could modify the association. Incident RCC case subjects and healthy control subjects were recruited from the University of Texas MD Anderson Cancer Center in Houston, Texas. Case subjects and control subjects were frequency matched. Epidemiologic data were collected by in-person interview. One hundred ninety single nucleotide polymorphisms (SNPs) from 22 genes in the mTOR pathway were extracted from previous genome-wide association studies. Logistic regression and regression spline were performed to obtain odds ratios (ORs). All statistical tests were two-sided. A total of 577 non-Hispanic white case subjects and 593 healthy control subjects were included. Obesity at age 20 years (OR = 1.92, 95% confidence interval [CI] = 1.05 to 3.50; P = .03) and age 40 years (OR = 2.03, 95% CI = 1.38 to 2.98; P < .001) and moderate (OR = 1.46, 95% CI = 1.02 to 2.09; P = .04) and massive weight gain (OR = 1.62, 95% CI = 1.10 to 2.39; P = .01) from age 20 to 40 years were each statistically significantly associated with increased RCC risk. Low physical activity was associated with a 4.08-fold increased risk. Among 190 SNPs in the mTOR pathway, six SNPs located in the AKT3 gene were statistically significantly associated with increased risk, and those with three or more unfavorable genotypes had a 1.72-fold increased risk of RCC. Obesity, weight gain, physical activity, and genetic variants in the mTOR pathway may individually and jointly influence susceptibility to RCC.
Phylogenetic Relationships within the Opisthokonta Based on Phylogenomic Analyses of Conserved Single-Copy Protein Domains
Authors: G. Torruella, R. Derelle, J. Paps, B. F. Lang, A. J. Roger, K. Shalchian-Tabrizi, I. Ruiz-Trillo
Journal: Molecular Biology and Evolution (2011)

Many of the eukaryotic phylogenomic analyses published to date were based on alignments of hundreds to thousands of genes. Frequently, in such analyses, the most realistic evolutionary models currently available are often used to minimize the impact of systematic error. However, controversy remains over whether or not idiosyncratic gene family dynamics (i.e., gene duplications and losses) and incorrect orthology assignments are always appropriately taken into account. In this paper, we present an innovative strategy for overcoming orthology assignment problems. Rather than identifying and eliminating genes with paralogy problems, we have constructed a data set comprised exclusively of conserved single-copy protein domains that, unlike most of the commonly used phylogenomic data sets, should be less confounded by orthology miss-assignments. To evaluate the power of this approach, we performed maximum likelihood and Bayesian analyses to infer the evolutionary relationships within the opisthokonts (which includes Metazoa, Fungi, and related unicellular lineages). We used this approach to test 1) whether Filasterea and Ichthyosporea form a clade, 2) the interrelationships of early-branching metazoans, and 3) the relationships among early-branching fungi. We also assessed the impact of some methods that are known to minimize systematic error, including reducing the distance between the outgroup and ingroup taxa or using the CAT evolutionary model. Overall, our analyses support the Filozoa hypothesis in which Ichthyosporea are the first holozoan lineage to emerge followed by Filasterea, Choanoflagellata, and Metazoa. Blastocladiomycota appears as a lineage separate from Chytridiomycota, although this result is not strongly supported. These results represent independent tests of previous phylogenetic hypotheses, highlighting the importance of sophisticated approaches for orthology assignment in phylogenomic analyses.
Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study
Authors: YY Koh, MH Lee, YH Sun, KW Sung, JH Chae
Journal: European Respiratory Journal (1997)

Increased airway responsiveness (AR) is frequently associated with bronchiectasis. Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities. This study was designed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR. Twenty five children with bronchiectasis, who had an increased AR (defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) <25 mg x mL(-1) evaluated by the dosimeter method), were randomized, double-blind into two parallel groups. Thirteen of the children were treated with roxithromycin (4 mg x kg(-1) b.i.d.) for 12 weeks and 12 received placebo. FEV1, sputum purulence and leucocyte scores were assessed every 3 weeks. To estimate AR, high-dose methacholine challenge tests were performed before and after treatment. On the dose-response curve to methacholine, PD20 and maximal response (two indices of AR) were measured. Changes in FEV1 were not observed during the course of the study in both groups. A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group. After 12 weeks of roxithromycin therapy, the geometric mean (range of 1 SD) of provocative cumulative dose producing a 20% fall in FEV1 (PD20) increased significantly (p<0.01) to 169.2 (83.2-344.2) breath units (BU) (1 BU denotes one inhalation of 1 mg x mL(-1) methacholine) and the mean+/-SD of maximal response decreased significantly (p<0.01) to 32.5+/-6.8%, as compared with the initial values (PD20 87.1 (47.3-160.4) BU; maximal response 40.9+/-7.4%). No significant changes in either parameter were observed in the placebo group. Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness. Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact.
Analysis of the nucleotide sequence of chromosome VI from Saccharomyces cerevisiae
Authors: Yasufumi Murakami, Masanori Naitou, Hiroko Hagiwara, Takehiko Shibata, Masashi Ozawa, Syun-ichi Sasanuma, Motoe Sasanuma, Yukari Tsuchiya, Eiichi Soeda, Kazushige Yokoyama, Masaaki Yamazaki, Hiroyuki Tashiro, Toshihiko Eki
Journal: Nature Genetics (1995)
Vasoconstrictor activities and bio-availabilities of seven proprietary corticosteroid creams assessed using a non-occluded multiple dosage regimen;clinical implications
Authors: B.W. BARRY, R. WOODFORD
Journal: British Journal of Dermatology (1977)

Journal Article Vasoconstrictor activities and bio‐availabilities of seven proprietary corticosteroid creams assessed using a non‐occluded multiple dosage regimen;clinical implications Get access B.W. BARRY, B.W. BARRY School of Pharmacy, Portsmouth Polytechnic, King Henry I Street, Portsmouth) Hants PO1 2DZ Search for other works by this author on: Oxford Academic Google Scholar R. WOODFORD R. WOODFORD School of Pharmacy, Portsmouth Polytechnic, King Henry I Street, Portsmouth) Hants PO1 2DZ Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 97, Issue 5, 1 May 1977, Pages 555–560, https://doi.org/10.1111/j.1365-2133.1977.tb14135.x Published: 01 May 1977
IgG immunoadsorption reduces systemic lupus erythematosus activity and proteinuria: a long term observational study
Authors: G H Stummvoll
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To analyse the effects of rigorous immunoglobulin removal by immunoadsorption (IAS) on proteinuria (primary outcome variable), disease activity (SIS, SLEDAI, ECLAM), and autoantibodies to double stranded DNA (anti-dsDNA) in active systemic lupus erythematosus (SLE). <b>Methods:</b> 16 patients with severe SLE and renal disease, in whom cyclophosphamide was contraindicated or failed to halt disease progression, were treated with IAS for 3 months. Patients achieving at least 20% improvement in two or more of the outcome measures were considered responders and offered a 9 months' extension period. <b>Results:</b> Within 3 months, 14 patients responded and 11 opted for an extension. Proteinuria decreased from 6.7 (4.6) g/day (mean (SD)) at baseline to 4.3 (3.5) g/day at 3 months and 2.9 (2.4) g/day at 12 months (p&lt;0.001). From baseline to 3 and 12 months, disease activity improved independently of scoring by SIS (15 (5) to 5 (2) and to 5 (2), p&lt;0.0001), SLEDAI (21 (7) to 5 (4) and to 5 (4), p&lt;0.0001), or ECLAM (7 (2) to 2 (1) and to 3 (1), p&lt;0.0001). Anti-dsDNA fell from 391 (647) IU/ml to 146 (218) and to 53 (50) IU/ml at 3 and 12 months, respectively. Steroids could be tapered from 117 (159) mg/day at baseline to 29 (17) mg/day at 3 months and 9 (2) mg/day at 12 months. IAS was not associated with an excess of infections. However, one patient died of septicaemia after 1 month of treatment. <b>Conclusion:</b> In this negatively selected cohort of patients with SLE, IAS was associated with a significant response shown by reduced proteinuria, improved global disease activity, decreased anti-dsDNA, and lower glucocorticoid dosages, suggesting therapeutic benefit.