tbuckley/cabot-search huggingface dataset:
Genome-wide assessment of imprinted expression in human cells
Authors: Lisanne Morcos, Bing Ge, Vonda Koka, Kevin CL Lam, Dmitry K Pokholok, Kevin L Gunderson, Alexandre Montpetit, Dominique J Verlaan, Tomi Pastinen
Journal: Genome biology (2011)

Abstract Background Parent-of-origin-dependent expression of alleles, imprinting, has been suggested to impact a substantial proportion of mammalian genes. Its discovery requires allele-specific detection of expressed transcripts, but in some cases detected allelic expression bias has been interpreted as imprinting without demonstrating compatible transmission patterns and excluding heritable variation. Therefore, we utilized a genome-wide tool exploiting high density genotyping arrays in parallel measurements of genotypes in RNA and DNA to determine allelic expression across the transcriptome in lymphoblastoid cell lines (LCLs) and skin fibroblasts derived from families. Results We were able to validate 43% of imprinted genes with previous demonstration of compatible transmission patterns in LCLs and fibroblasts. In contrast, we only validated 8% of genes suggested to be imprinted in the literature, but without clear evidence of parent-of-origin-determined expression. We also detected five novel imprinted genes and delineated regions of imprinted expression surrounding annotated imprinted genes. More subtle parent-of-origin-dependent expression, or partial imprinting, could be verified in four genes. Despite higher prevalence of monoallelic expression, immortalized LCLs showed consistent imprinting in fewer loci than primary cells. Random monoallelic expression has previously been observed in LCLs and we show that random monoallelic expression in LCLs can be partly explained by aberrant methylation in the genome. Conclusions Our results indicate that widespread parent-of-origin-dependent expression observed recently in rodents is unlikely to be captured by assessment of human cells derived from adult tissues where genome-wide assessment of both primary and immortalized cells yields few new imprinted loci.
Übersense Coach app for sport medicine? Slow motion video analysis (Mobile App User Guide)
Authors: Richard Weiler
Journal: British Journal of Sports Medicine (2015)

Sports medicine, gait analysis and sports biomechanics

Apple (iOS 7.0 or later); Android (versions 4.3 and up)

Free

Ubersense is primarily marketed as a coaching tool to help improve athlete performance by improving technique and movement, through movement and technique analysis with feedback of form, during training, competition or game, and allowing comparison to self, elite and professional athletes. The app requires the user to video record any movement, such as a run, throw, tennis serve or golf swing, and to analyse each section of movement frame-by-frame and from any angle or …
Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence.
Authors: Judith A Staples, Anne-Louise Ponsonby, Lynette L-Y Lim, Anthony J McMichael
Journal: Environmental Health Perspectives (2002)

The apparent immune-suppressive effect of ultraviolet radiation (UVR) has suggested that this environmental exposure may influence the development of immune-related disorders. Self-reported prevalence rates of type 1 diabetes mellitus, rheumatoid arthritis (RA), eczema/dermatitis, and asthma, from the 1995 Australian National Health Survey, were therefore examined by latitude and ambient level of UVR. A positive association of type 1 diabetes mellitus prevalence was found with both increasing southern latitude of residence (r = 0.77; p = 0.026) and decreasing regional annual ambient UVR (r= -0.80; p = 0.018); a 3-fold increase in prevalence from the northernmost region to the southernmost region was evident. In contrast, asthma correlated negatively with latitude (r = -0.72; p = 0.046), although the change in asthma prevalence from the north to the south of Australia was only 0.7-fold. For both RA and eczema/dermatitis, there were no statistically significant associations between latitude/UVR and disease prevalence. These ecologic data provide some support for a previously proposed beneficial effect of UVR on T-helper 1-mediated autoimmune disorders such as type 1 diabetes. The inverse association of type 1 diabetes prevalence with UVR is consistent with that previously reported for another autoimmune disease, multiple sclerosis, in Australia, and also with type 1 diabetes latitudinal gradients in the Northern Hemisphere. The finding also accords with photoimmunologic evidence of UVR-induced immunosuppression and may suggest a beneficial effect of UVR in reducing the incidence of such autoimmune conditions. In light of this study, analytic epidemiologic studies investigating risk of immune disorders in relation to personal UVR exposure in humans are required.
Regional blood flow redistribution due to acetate.
Authors: D R Buyer, R L Krahmer, A H Lau, H C Wang, J L Ferguson, J T Daugirdas
Journal: Journal of the American Society of Nephrology (1993)

There is little information about the effects of acetate on regional blood flow in unanesthetized animals. Isosmolal sodium acetate or saline was infused at a rate of 250 mumol/kg.min into conscious rats such that, in the acetate group, plasma acetate levels averaged 2.06 +/- 0.23 mM. Sequential injections of tracer-tagged microspheres were used to determine the effect of acetate infusion on cardiac output, total peripheral vascular resistance, and various organ blood flow rates. At this infusion level, acetate had no discernible effect on either central hemodynamics or arterial blood gases. However, there was marked alteration of regional organ perfusion. After 5 min of infusion, acetate (relative to control) increased blood flow markedly to the splanchnic bed (+40 +/- 6.1%), including all individual splanchnic organs except for the stomach. Acetate also increased blood flow to the heart (+33 +/- 5.2%) and kidneys (+29 +/- 5.4%); all P < 0.05. Acetate had no specific effect on total cerebral blood flow or on regional brain circulations. Acetate had no effect on flow to skeletal muscle (-30 +/- 11%; P = not significant) or fat (-5 +/- 6.3%; P = 0.097), although flow to muscle tended to decrease. These data suggest that low plasma levels of acetate, which do not alter total peripheral resistance, cause a marked redistribution of blood flow to the splanchnic organs and to the kidneys. Brain blood flow is unaffected.
Attention Bias to Threat in Maltreated Children: Implications for Vulnerability to Stress-Related Psychopathology
Authors: Daniel S Pine, Karin Mogg, Brendan P Bradley, LeeAnne Montgomery, Christopher S Monk, Erin McClure, Amanda E Guyer, Monique Ernst, Dennis S Charney, Joan Kaufman
Journal: American Journal of Psychiatry (2005)

Previous research in adults implicates attention bias in posttraumatic stress disorder (PTSD). To study attention bias in children, the authors used picture-based versions of the visual-probe attention bias task previously used with adults. They tested the hypothesis that attention bias to threatening facial photographs is associated with maltreatment and PTSD.A visual-probe task that manipulated threat levels was used to test 34 children who had been maltreated and 21 children who had not been maltreated. The visual-probe task involved showing photographs of actors with faces depicting neutral, angry/threatening, or happy expressions for 500 msec each.Attention bias away from threat was associated with severity of physical abuse and diagnosis of PTSD. This association reflected the tendency for high levels of abuse or PTSD to predict attention avoidance of threatening faces.Previous studies examined the engagement of specific brain regions associated with attention orientation to angry/threatening faces. The current study used similar methods to document associations between attention bias and maltreatment in children. This sets the stage for studies examining relationships in children among perturbed brain function, psychopathology, attention bias, and maltreatment.
Impact of FOLFIRINOX Compared With Gemcitabine on Quality of Life in Patients With Metastatic Pancreatic Cancer: Results From the PRODIGE 4/ACCORD 11 Randomized Trial
Authors: Sophie Gourgou-Bourgade, Caroline Bascoul-Mollevi, Françoise Desseigne, Marc Ychou, Olivier Bouché, Rosine Guimbaud, Yves Bécouarn, Antoine Adenis, Jean-Luc Raoul, Valérie Boige, Jocelyne Bérille, Thierry Conroy
Journal: Journal of Clinical Oncology (2012)

To compare the quality of life (QoL) of patients receiving oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) or gemcitabine as first-line chemotherapy and to assess whether pretreatment QoL predicts survival in patients with metastatic pancreatic cancer.Three hundred forty-two patients with performance status 0 or 1 were randomly assigned to receive FOLFIRINOX (oxaliplatin, 85 mg/m(2); irinotecan, 180 mg/m(2); leucovorin, 400 mg/m(2); and fluorouracil, 400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-hour continuous infusion, once every 2 weeks) or gemcitabine 1,000 mg/m(2) weekly for 7 of 8 weeks and then weekly for 3 of 4 weeks. QoL was assessed using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire C30 every 2 weeks.Improvement in global health status (GHS; P < .001) was observed in the FOLFIRINOX arm and improvement in emotional functioning (P < .001) was observed in both arms, along with a decrease in pain, insomnia, anorexia, and constipation in both arms. A significant increase in diarrhea was observed in the FOLFIRINOX arm during the first 2 months of chemotherapy. Time until definitive deterioration ≥ 20 points was significantly longer for FOLFIRINOX compared with gemcitabine for GHS, physical, role, cognitive, and social functioning, and six symptom domains (fatigue, nausea/vomiting, pain, dyspnea, anorexia, and constipation). Physical functioning, constipation, and dyspnea were independent significant prognostic factors for survival with treatment arm, age older than 65 years, and low serum albumin.FOLFIRINOX significantly reduces QoL impairment compared with gemcitabine in patients with metastatic pancreatic cancer. Furthermore, baseline QoL scores improved estimation of survival probability when added to baseline clinical and demographic variables.
Chiropractic in from the cold?
Authors: A G Hocken
Journal: BMJ (1980)

Sid Scales has an astute political wit, a social perception, and a comprehension of his fellow Kiwi which sets him high as a graphic commentator in the Otago Daily Times. Scales recently picked upon a quotation from the report of the Commission of Inquiry into Chiropractic in New Zealand, which said: In the public interest there must be no impediment to full professional co-operation between chiropractors and medical practitioners. His drawing showed a commission benignly smirking behind the chairman's comment as the black-coated, striped-trousered figure strode from the bench carrying his black bag in his hand and his nose in the air, You ought to see a chiropractor about that stiff neck of yours, doctor!
Correspondence re: Raida, M. et al., Prevalence of a Common Point Mutation in the Dihydropyrimidine Dehydrogenase (DPD) Gene within the 5-Splice Donor Site of Intron 14 in Patients with Severe 5-Fluorouracil (5-FU)-related Toxicity Compared with Controls. Clin. Cancer Res., 7: 2832-2839, 2001.
Authors: Federico Innocenti, Mark J. Ratain
Journal: Clinical Cancer Research (2002)

Raida et al . [(1)][1] , in the September 2001 issue of Clinical Cancer Research, investigated the genetic basis of dihydropyrimidine dehydrogenase deficiency in cancer patients who developed grade 3–4 toxicity after 5-FU[2][2] -containing regimens. Twenty-five patients were genotyped for the exon
Strongyloidiasis in ex-Far East prisoners of war.
Authors: G V Gill, D R Bell, H A Reid
Journal: BMJ (1977)

Strongyloidiasis in ex-Far East prisoners of war Infestations with the nematode worm Strongyloides stercoralis are common in the tropics, and may persist for many years.Although often asymptomatic,.infestationsmay be associated with diarrhoea or skin lesions.Our experience suggests that this eruption is quite common among ex-Far East prisoners of war, and we have therefore investigated and treated a group of these patients with encouraging results. CommentWe have found this technique of female sterilisation easy to learn and technically as simple as laparoscopic tubal diathermy.It seems to
Hepatitis B virus Dane particles bind to human plasma apolipoprotein H
Authors: Ilias Stefas, Marcel Rucheton, Arnaud Dupuy D'Angeac, Christine Morel-Baccard, Jean M. Seigneurin, Jean P. Zarski, Marianne Martin, Martine Cerutti, Jean Pierre Bossy, Dorothée Missé, Hubert Graafland, Francisco Veas
Journal: Hepatology (2001)

Human apolipoprotein H (apo H) was found to bind specifically to hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV)–infected individuals. We used recombinant HBsAg proteins to analyze HBV domains recognized by apo H. We showed that the myristylated pre–S1 domain of HBsAg strongly interacted with apo H. This binding involved phospholipid components of the HBV envelope because their removal by detergent prevented apo H–HBsAg interaction. The opposite effects of iron and zinc metal ions on binding suggest that the oxidation of phospholipids also affects apo H–HBsAg interaction. After fractionation of viral particles on a sucrose gradient, and their addition to microtiter plates coated with apo H or anti–HBsAg, we observed that the maximal anti–HBsAg capture activity corresponded to a sucrose concentration of 36%, whereas the maximal apo H capture activity corresponded to a concentration of 39%. Electron microscopy and polymerase chain reaction (PCR) Southern blot studies of these fractions showed that the fraction with maximal apo H binding predominantly contained full Dane particles. Finally, we studied apo H–HBsAg binding relative to the presence of hepatitis B virus markers and observed that apo H binding activity for HBsAg was higher in sera from patients in the active virus replication phase.
Alterations in enzymatic functions in hepatocytes and hepatocellular carcinomas fromRas-transduced livers resemble the effects of insulin
Authors: R V Pearline, Y Lin, K J Shen, E M Brunt, W M Bowling, D G Hafenrichter, S Kennedy, M W Flye, K P Ponder
Journal: Hepatology (1996)

An understanding of how oncogenes affect differentiated liver functions might lead to improved treatments for liver cancer or other disorders where liver–specific functions are compromised. A retroviral vector that coexpressed β–galactosidase (β–gal) and activated Ras genes ( Ras–gal ) was transduced into a small fraction of adult rat hepatocytes in vivo . Hepatocytes from Ras–gal –transduced diethylnitrosamine– untreated livers and hepatocellular carcinomas (HCC) from Ras–gal – transduced diethylnitrosamine–treated rats were analyzed for liver functions by performing histochemical assays on liver sections. Ras–gal – transduced hepatocytes failed to express gluconeogenic, ketogenic, and urea pathway enzymes. In contrast, several enzymes involved in fat synthesis were strongly activated, and microvesicular fat accumulated. These metabolic changes are induced in normal livers by insulin, a hormone that activates p21–ras . The deregulation of p21–ras may inhibit these liver–specific functions and may induce fat synthesis in both malignant and nonmalignant liver diseases. Furthermore, treatment with drugs that inhibit the attachment of p21–ras to the plasma membrane might reverse these changes. The alterations in enzymatic functions in the HCCs were similar to those observed in the hepatocytes, although each of the two cancers had a region that abruptly lost its expression of liver–specific enzymes and acquired the expression of genes that are more characteristic of oval or bile ductule cells. This suggests that a single genetic event in a malignant cell may dramatically alter its apparent phenotype. The identification of this putative gene might lead to insights into the regulation of the phenotype of normal cells in the liver.
Prospective Evidence of a Circadian Rhythm for Out-of-Hospital Cardiac Arrests
Authors: Robert L. Levine
Journal: JAMA (1992)

<h3>Objectives.</h3> —Published studies have indicated a circadian rhythm in the occurrence of sudden cardiac death. However, these studies have involved either retrospective analyses of death certificates or analyses of data collected during studies of pharmacologic agents in selected populations. <h3>Purpose.</h3> —To determine whether a circadian pattern could be clearly demonstrated in a prospective study of out-of-hospital sudden cardiac death in a large, unselected population. <h3>Design.</h3> —All adult cases of sudden death of presumed primary cardiac cause from a large urban population were prospectively evaluated over a 12-month period. The incidence of sudden cardiac death was analyzed using harmonic regression of the data tabulated by hour of the day. <h3>Results.</h3> —During the year of study, 1019 consecutive primary cardiac arrests were analyzed. A significant circadian pattern was found (P&lt;.0001) with the frequency of cardiac arrests increasing dramatically from 6 AM until noon. <h3>Conclusions.</h3> —This prospective study of out-of-hospital cardiac arrest confirms the existence of a circadian rhythm. These data have important implications for future investigations concerning the pathophysiology of sudden cardiac deaths. (<i>JAMA</i>. 1992;267:2935-2937)
Kistrin, a polypeptide platelet GPIIb/IIIa receptor antagonist, enhances and sustains coronary arterial thrombolysis with recombinant tissue-type plasminogen activator in a canine preparation.
Authors: T Yasuda, H K Gold, R C Leinbach, H Yaoita, J T Fallon, L Guerrero, M A Napier, S Bunting, D Collen
Journal: Circulation (1991)

BACKGROUND Kistrin is a 68-amino acid polypeptide from the venom of the Malayan pit viper Agkistrodon rhodostoma, which inhibits the platelet GPIIb/IIIa receptor. Its effect on thrombolysis, reocclusion, and bleeding associated with administration of recombinant tissue-type plasminogen activator (rt-PA) was studied in a canine model of coronary artery thrombosis. METHODS AND RESULTS Coronary patency was monitored for 2 hours by ultrasonic flow probe and repeated coronary angiography. The rt-PA was given as 0.45-mg/kg bolus injections at 15-minute intervals until recanalization or to a maximum of four boluses. Four groups of four or five dogs were studied: a control group that received intravenous heparin (4,000-unit bolus and 1,000 units each hour) and three groups that received heparin and 0.48, 0.24, or 0.12 mg/kg kistrin, administered as a 10% bolus injection and an infusion during a 60-minute period. In the control group, reflow occurred in four of five dogs within 37 +/- 47 minutes but was followed by cyclic reflow and reocclusion. Kistrin at a dose of 0.48 and 0.24 mg/kg reduced the time to reflow to 6 +/- 5 and 10 +/- 3 minutes, respectively, and abolished reocclusion. With 0.12 mg/kg kistrin, reflow occurred in all four animals, within 27 +/- 23 minutes, and reocclusion occurred in two animals. Kistrin induced a dose-related prolongation of the template bleeding time: with 0.48 mg/kg kistrin, the bleeding time was prolonged from 3.8 +/- 1.3 minutes before infusion to 29 +/- 2 minutes during infusion, but it was shortened to 8.3 +/- 2.6 minutes at 90 minutes after the end of infusion. Kistrin also caused a dose-related inhibition of platelet aggregation with ADP and collagen: with 0.48 mg/kg kistrin, platelet aggregation was abolished during the infusion but had partially recovered toward the end of the observation period. Pathological examination of recanalized coronary arterial segments of dogs given 0.48 or 0.24 mg/kg kistrin revealed widely patent arteries with some platelets layered on the damaged intimal surface. CONCLUSIONS Kistrin increases the rate and extent of thrombolysis with a reduced dose of rt-PA, and it prevents reocclusion. At an effective dose, it is associated with a transient prolongation of the bleeding time and inhibition of platelet aggregation. Kistrin may offer promise as adjunctive treatment to thrombolytic agents in patients with acute myocardial infarction.
Ependymoma stem cells are highly sensitive to temozolomide in vitro and in orthotopic models
Authors: D. Meco, T. Servidei, G. Lamorte, E. Binda, V. Arena, R. Riccardi
Journal: Neuro-Oncology (2014)

Ependymoma management remains challenging because of the inherent chemoresistance of this tumor. To determine whether ependymoma stem cells (SCs) might contribute to therapy resistance, we investigated the sensitivity of ependymoma SCs to temozolomide and etoposide. The efficacies of the two DNA damaging agents were explored in two ependymoma SC lines in vitro and in vivo models. Ependymoma SC lines were highly sensitive to temozolomide and etoposide in vitro, but only temozolomide impaired tumor-initiation properties. Consistently, temozolomide but not etoposide showed significant antitumoral activity on ependymoma SC-driven subcutaneous and orthotopic xenografts by reducing the mitotic fraction. In vitro temozolomide at the EC50 (10 µM) induced accumulation of cells in the G2/M phase that was unexpectedly accompanied by downregulation of p27 and p21 without modulation of full-length p53 (FLp53). Differentiation-committed ependymoma SCs acquired resistance to temozolomide. Inhibition of proliferation was partly due to apoptosis, that occurred earlier in differentiated cells as compared to neurospheres. The activation of apoptosis correlated with an increase in p53β/γ isoforms without modulation of FLp53 under both serum-free and differentiation-promoting media. Incubation of cells in both conditions with temozolomide resulted in increased glioneuronal differentiation exhibiting elevated glial fibrillary acidic protein, galactosylceramidase, and βIII-tubulin expression compared to untreated controls. O6-methylguanine DNA methyltransferase (MGMT) transcript levels were very low in SCs, and were increased by treatment and, epigenetically, by differentiation through MGMT promoter unmethylation. Ependymoma growth might be impaired by temozolomide through preferential depletion of a less differentiated, more tumorigenic, MGMT-negative cell population with stem-like properties.
Potential association of muscarinic receptor 3 gene variants with primary Sjogren's syndrome
Authors: S. Appel, S. Le Hellard, O. Bruland, J. G. Brun, R. Omdal, G. Kristjansdottir, E. Theander, G. Nordmark, M. Kvarnstrom, P. Eriksson, L. Ronnblom, M. Wahren-Herlenius, R. Jonsson
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Primary Sjögren9s syndrome (pSS) is characterised by a chronic inflammation of exocrine glands. Salivary gland infiltrates, however, do not correlate well with disease symptoms, and a primary role for the salivary gland parenchyma in disease development has been suggested. Specifically, dysfunction of exocrine pathways involving the muscarinic receptor 3 (CHRM3) has been indicated. <h3>Objective</h3> To investigate possible genetic divergence in the <i>CHRM3</i> gene in patients with pSS. <h3>Methods</h3> 530 patients with pSS and 532 controls from a combined Swedish and Norwegian cohort were genotyped for 84 single nucleotide polymorphisms (SNPs) distributed throughout <i>CHRM3</i>. <h3>Results</h3> Genetic association was observed with five SNPs localised in intron 3 and 4 of <i>CHRM3,</i> the strongest being rs7548522 (minor allele frequency = 0.06, OR=1.93, 95% CI (1.24 to 3.01); p=0.0033). In addition, clinical parameters, including focus score, abnormal Schirmer9s test and presence of autoantibodies, were associated with different SNPs in <i>CHRM3</i>. <h3>Conclusion</h3> The study demonstrates a novel association of <i>CHRM3</i> polymorphisms with pSS, suggesting a functional role for CHRM3 and the salivary gland parenchyma in the pathogenesis of pSS.