tbuckley/cabot-search huggingface dataset:
Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival
Authors: Anita Sveen, Trude H Ågesen, Arild Nesbakken, Torleiv O Rognum, Ragnhild A Lothe, Rolf I Skotheim
Journal: Genome Medicine (2011)

Colorectal cancer (CRC) is a heterogeneous disease that, on the molecular level, can be characterized by inherent genomic instabilities; chromosome instability and microsatellite instability. In the present study we analyze genome-wide disruption of pre-mRNA splicing, and propose transcriptome instability as a characteristic that is analogous to genomic instability on the transcriptome level.Exon microarray profiles from two independent series including a total of 160 CRCs were investigated for their relative amounts of exon usage differences. Each exon in each sample was assigned an alternative splicing score calculated by the FIRMA algorithm. Amounts of deviating exon usage per sample were derived from exons with extreme splicing scores.There was great heterogeneity within both series in terms of sample-wise amounts of deviating exon usage. This was strongly associated with the expression levels of approximately half of 280 splicing factors (54% and 48% of splicing factors were significantly correlated to deviating exon usage amounts in the two series). Samples with high or low amounts of deviating exon usage, associated with overall transcriptome instability, were almost completely separated into their respective groups by hierarchical clustering analysis of splicing factor expression levels in both sample series. Samples showing a preferential tendency towards deviating exon skipping or inclusion were associated with skewed transcriptome instability. There were significant associations between transcriptome instability and reduced patient survival in both sample series. In the test series, patients with skewed transcriptome instability showed the strongest prognostic association (P = 0.001), while a combination of the two characteristics showed the strongest association with poor survival in the validation series (P = 0.03).We have described transcriptome instability as a characteristic of CRC. This transcriptome instability has associations with splicing factor expression levels and poor patient survival.
Characterization of the aminopeptidase activity of epidermal leukotriene A4 hydrolase against the opioid dynorphin fragment 1-7
Authors: J.B. NISSEN, L. IVERSEN, K. KRAGBALLE
Journal: British Journal of Dermatology (2006)

Leukotriene A4 hydrolase is a bifunctional cytosolic enzyme, which both hydrolyses leukotriene A4 (LTA4) into leukotriene B4 (LTB4) and exerts aminopeptidase activity against opioid peptides. In the present study we have investigated whether the peptides angiotensin I and II, bradykinin, kallidine, histamine, dynorphin fragment 1-7 and substance P can act as substrates for epidermal and neutrophil LTA4 hydrolase. Among the tested substrates, dynorphin fragment 1-7 was found to be the best substrate for the enzyme. The aminopeptidase activity of epidermal and neutrophil LTA4 hydrolase against dynorphin fragment 1-7 was further characterized. The enzyme was purified from human epidermis and human neutrophils by anion exchange chromatography (Q-Sepharose) and affinity chromatography on a column with the LTA4 hydrolase inhibitor bestatin coupled to AH-Sepharose. The incubation of the dynorphin fragment 1-7 with LTA4 hydrolase resulted in the formation of tyrosine. The presence of the N-terminal amino acid tyrosine is essential for the interaction of opioids with their receptors, and this finding indicates that the LTA4 hydrolase can inactivate dynorphin fragment 1-7. After the two purification steps no other aminopeptidases acting at the N-terminal tyrosine of dynorphin fragment 1-7 was present in the preparation. This was demonstrated by the abolishment of the degradation at the N-terminal end of dynorphin fragment 1-7 when preincubating the enzyme preparation with LTA4 before the incubation with the dynorphin fragment 1-7. The abolishment of the aminopeptidase activity shows that activation of the hydrolase part of the enzyme, with conversion of LTA4 into the potent proinflammatory compound LTB4, results in an inhibition of the aminopeptidase activity of the enzyme. As a result, the catabolism of dynorphin fragment 1-7 and probably of other opioid peptides is inhibited, resulting in sustained biological effects of these opioids. This phenomenon may be important for the maintenance of inflammation in skin conditions, such as psoriasis and atopic dermatitis, in which LTB4 is formed.
Segmental and Global Subclasses of Class IV Lupus Nephritis Have Similar Renal Outcomes
Authors: Catharina M. Haring, Anke Rietveld, Jan A.J.G. van den Brand, Jo H.M. Berden
Journal: Journal of the American Society of Nephrology (2011)

Whether renal outcomes differ between the segmental and global subclasses of diffuse proliferative (class IV) lupus nephritis is unknown. In this meta-analysis, we searched the literature in MEDLINE, EMBASE, five registries of clinical trials, and selected cohort studies and randomized, controlled trials that used the 2003 International Society of Nephrology and Renal Pathology Society classification of lupus nephritis in adult patients. Our endpoint was the composite of doubling of serum creatinine concentration or ESRD. In the eight studies included in the final analysis, the incidence of this endpoint varied between 0% and 67%. A funnel plot and Egger's test did not suggest significant heterogeneity. The meta-analysis did not support a significant difference in renal outcome between the segmental (IV-S) and global (IV-G) subclasses (relative risk for class IV-G versus IV-S, 1.08; 95% confidence interval, 0.68–1.70). Meta-regression did not suggest that ethnicity or duration of follow-up influenced the association between histologic class and renal risk. In conclusion, the rate of doubling of serum creatinine concentration or of ESRD did not differ between patients with class IV-S and those with IV-G lupus nephritis.
Persistence of Restrictions in Quality of Life From the First to the Third Year After Diagnosis in Women With Breast Cancer
Authors: Volker Arndt, Henrike Merx, Christa Stegmaier, Hartwig Ziegler, Hermann Brenner
Journal: Journal of Clinical Oncology (2005)

To assess whether detriments in quality of life (QOL) among women with breast cancer persist over years.QOL was assessed in a population-based cohort of 314 women with breast cancer from Saarland (Germany) 1 and 3 years after diagnosis and compared internally and with reference data from the general population.Three years after diagnosis, deficits in QOL were still apparent for role, emotional, cognitive, and social functioning and for the symptoms of insomnia, fatigue, dyspnea, and financial difficulties. Differences between breast cancer patients and women from the general population were predominantly found in younger ages. Compared with the QOL scores measured 1 year after diagnosis, only minor functional changes were observed, but recurrence of breast cancer during the follow-up interval had a deleterious effect on QOL.Deficits in role, emotional, cognitive, and social functioning persist over years in women with breast cancer and predominantly affect younger patients.
Play structure of top female volleyball players: explorative factorial approach
Authors: G Nesic, M Sikimic, V Ilic, T Stojanovic
Journal: British Journal of Sports Medicine (2011)

Background Volleyball, as a sports game, requires from the players high level preparedness with respect to all the motor abilities, as well as an efficient execution of necessary technical and tactical game elements. Objective The aim of this research is to establish characteristics of the competitive activity structure in female volleyball at European Senior Championships in Bulgaria 2001, in Turkey 2003 and in Croatia 2005. Design, setting and methods An overall of 48 games of all three championships were analyzed. Comparative analysis of the latent competitive activity structure of female volleyball players was performed by factorial data analysis (factor rotation in Varimax solution). Results In the latent space of competitive analysis, three independent factors were isolated, justifying 73.76% of overall system variance. Factor 1 (space-time factor) explains 36.12% of overall variance and is defined by the following manifest variables: jumps (0.934), active (0.921) and passive (0.906) time of the game and strikes at ball (0.893). Factor 2 (situational precision) explains 21.46% of all variance and is defined by the following manifest variables: efficiency coefficient (KE) of serve receiving (0.940), followed by KE of ball raising for attack (0.829), and the lowest KE is manifested in field defence (0.815). Factor 3 (technical-tactical efficiency) in latent space of competitive activity explains 16.19% of all variance and is defined by the following manifest realization of technical-tactical elements (0.685), and the smallest and negative KE drops in the variables: KE of attack (0.819), serve KE (0.803), KE block (0.711), success in field defence (−0.558). Conclusions All the variables significantly contribute to defining of isolated factors, but the greatest contribution belongs to jumps, active and passive time of the game and strikes at the ball, which is logical, because these variables are constant during the entire game. Other variables, that is, isolated factors of situational precision and factors of technical-tactical efficiency, are expressed through them.
Does hyperhomocysteinaemia contribute to gastric carcinogenesis in Helicobacter pylori infected patients
Authors: L Peyrin-Biroulet, Jean-Louis Guéant
Journal: Gut (2007)

In a recent issue of Gut , Marino et al showed that eradication of Helicobacter pylori resulted in increased levels of vitamin B-12 (cobalamin) and decreased levels of plasma homocysteine in elderly patients ( Gut 2007; 56 :469–74), confirming preliminary reports.1 The authors recall that cobalamin deficiency is associated with H pylori infection and is a major cause of hyperhomocysteinaemia in the general population.

Global DNA hypomethylation, which is associated with hyperhomocysteinaemia,2 is an epigenetic event often found in tumour cells.3 The homocysteine raising effect of H pylori may thus promote gastric carcinogenesis. Consistently, a recent study showed that hyperhomocysteinaemia may increase the risk of developing gastric cancer in a Chinese population.4 Along with Marino’s results, these findings may provide new insights in our understanding of H pylori related gastric carcinogenesis.

One question remains open: Is eradication of H pylori the best way to prevent gastric cancer? The conclusion of the Maastricht III consensus report was that “Eradication of H pylori infection has the potential to reduce the risk …
Expression of the oxytocin receptor in relation to steroid receptors in the uterus of a primate model, the marmoset monkey
Authors: A Einspanier, A Bielefeld, J H Kopp
Journal: Human Reproduction Update (1998)

The dynamics of the receptors for oestrogen (ER), progesterone (PR) and oxytocin (OTR) in the marmoset uterus have been analysed throughout the entire cycle and early pregnancy. Uteri obtained during the early, mid/late and late proliferative phase, and the early, mid and late secretory phase and early pregnancy were examined by immunohistochemistry (OTR, ER, PR) and autoradiography (OTR). A massive upregulation of the ER in the cell nuclei of glandular epithelium and stromal cells during the mid proliferative phase was succeeded by a declining staining intensity and positively stained cell number in the secretory phase. PR immunoreactivity increased in the late proliferative phase and early secretory phase, mainly within the cell nuclei, and then declined in both intensity and cell number towards the mid to late secretory phase. Myometrium showed a similar staining pattern for the steroid receptors. OTR were expressed weakly in stroma throughout the entire cycle, increasing slightly in the secretory phase. Glandular epithelium showed positive staining only during the periovulatory period. Myometrial OTR expression was weak during the proliferative phase, increased towards the secretory phase, and was maximal in the late secretory phase. Myometrial tissue adjacent to endometrium was most strongly stained. A cyclic shift evidently occurred in the pattern of steroid receptors, perhaps reflecting the steroid environment or the luteinizing hormone increase associated with ovulation.
Response to Letter Regarding Article, “Greater Clinical Benefit of More Intensive Oral Antiplatelet Therapy With Prasugrel in Patients With Diabetes Mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel: Thrombolysis in Myocardial Infarction 38”
Authors: Stephen D. Wiviott, Eugene Braunwald, Sabina A. Murphy, Carolyn H. McCabe, Elliott M. Antman, Dominick J. Angiolillo, Simha Meisel, Anthony J. Dalby, Freek W.A. Verheugt, Shaun G. Goodman, Ramon Corbalan, Drew A. Purdy
Journal: Circulation (2009)
Long-Term Survival and Competing Causes of Death in Patients With Early-Stage Hodgkin’s Disease Treated at Age 50 or Younger
Authors: Andrea K. Ng, M. Patricia Bernardo, Edie Weller, Kendall H. Backstrand, Barbara Silver, Karen C. Marcus, Nancy J. Tarbell, Jonathan Friedberg, George P. Canellos, Peter M. Mauch
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To analyze the long-term survival and the pattern and timing of excess mortality in patients with early-stage Hodgkin’s disease. PATIENTS AND METHODS: Between 1969 and 1997, 1,080 patients age 50 or younger were treated for clinical stage IA to IIB Hodgkin’s disease. Overall survival was determined, and prognostic factors were assessed. Relative risk and absolute excess risk (AR) of mortality were calculated for the entire cohort and by prognostic groups (on the basis of B symptoms, mediastinal status, and number of sites, modified from the European Organization for Research and Treatment of Cancer). RESULTS: The median follow-up was 12 years. The 15- and 20-year Kaplan-Meier survival estimates were 84% and 78%, respectively. Cox proportional hazards models showed that number of involved sites (P = .006), mediastinal status (P = .02), and histology (P = .02) were independent predictors of death from all causes. The AR of mortality in patients with a favorable prognosis increased over time, whereas for those with an unfavorable prognosis, the AR peaked in the first 5 years, predominantly from Hodgkin’s disease. The relative risk of mortality from all causes, causes other than Hodgkin’s disease, second tumors, and cardiac disease remained significantly elevated more than 20 years after treatment. CONCLUSION: Patients treated for early-stage Hodgkin’s disease have a sustained excess mortality risk despite good control of the disease. Treatment reduction efforts in patients with early-stage, favorable-prognosis disease should continue, but for patients with an unfavorable prognosis, modified treatment may not be advisable. The excess mortality noted beyond two decades underscores the importance of long-term follow-up care in patients treated for Hodgkin’s disease.
Effects of neuromuscular electrical stimulation of the knee extensor muscles on muscle soreness and different serum parameters in young male athletes: preliminary data
Authors: Carina Zorn, Thomas Szekeres, Mohammad Keilani, Veronika Fialka-Moser, Richard Crevenna
Journal: British Journal of Sports Medicine (2007)

Aim: To evaluate the effects of neuromuscular electrical stimulation (NMES) on muscle soreness and on a variety of serum parameters during and after NMES of knee extensor muscles of young, well trained subjects over a study period of 96 h. Methods: Five male cyclists were included in this clinical observation. NMES (biphasic, asymmetric impulses) was applied through surface electrodes to both knee extensor muscles of each subject for 30 min. To determine changes in serum concentration of muscle proteins, blood samples were drawn at defined measure points before and after NMES. Muscle soreness was evaluated using a visual analogue scale at all measure points. Results: There was a maximum (p&lt;0.05) for “muscle pain” during stimulation but no significant changes could be detected after the stimulation period. Serum creatine kinase showed a peak with a significant increase (p&lt;0.05) 24 h after NMES. Serum lactate levels only increased slightly (p = 0.08) during NMES. Conclusions: Although the changes of blood parameters measured in the present work correspond to those reported in the literature on eccentric strength training, no delayed onset muscle pain could be detected. Further studies should be carried out, also investigating different stimulation protocols in non-trained healthy subjects and in patients with less muscle mass.
New US drama outrages plastic surgeons
Authors: J. Hopkins Tanne
Journal: BMJ (2003)

Imagine that you are a hotshot Miami plastic surgeon and you've just had an unfortunate—well, fatal—incident performing liposuction on a South American drug dealer who paid you cash upfront. Why the disaster? You were dumb enough to let the guy's brother into the operating room (for even more cash), where he went berserk. Would you dump the corpse into a Florida swamp? Furthermore, would you know enough to tie hams to the victim, because alligators love pork?

Consider that you refuse to do free work on a kid who needs skin grafts for burns. Or that yourpartner picks up a gorgeous woman in a bar, has throbbing sex with her, and then persuades her in the clear light of morning that she needs work on her forehead, her eyelids, her cheekbones, her breasts, and her tummy.

No wonder America's plastic surgeons are annoyed. These scenarios come straight from Nip/Tuck , a new US television programme featuring two plastic surgeon partners that was …
Defining ‘coeliac’: Oslo<i>Accord—</i>or not?
Authors: Michael N Marsh
Journal: Gut (2013)

The Oslo report1 favours abandoning long-accumulated baggage— ‘typical’ , ‘atypical’ , ‘non-classical’ , ‘active’ , ‘silent’ , ‘potential’ . But has Oslo bequeathed us greater definitional incisiveness than either Hawkey2 or Sleisenger and Fordtran3?

First, ‘chronic’?—Why not life-long ? ‘Precipitated’—meaning sudden onset?: either when alleged times to diagnosis are ∼10 years or gluten has been ingested for over 60 years? Why not caused ? And ‘enteropathy’? Are there hints here of persisting atavistic habituation: ‘coeliac disease is an intrinsic disorder of jejunum’? Mucosal involvement reflects regional exposure—jejunum, ileum or rectum,4 predicated on intestinal (mesenteric) immune system physiology.

This gives: ‘… a life-long , genetically-determined syndrome caused by gluten ingestion , eliciting a spectrum of (duodenal/jejunal) mucosal changes , and giving rise to symptoms …
Post-immunisation gastritis and Helicobacter infection in the mouse: a long term study
Authors: P Sutton
Journal: Gut (2001)

Helicobacter pylori is a major cause of peptic ulcers and gastric cancer. Vaccine development is progressing but there is concern that immunisation may exacerbate Helicobacter induced gastritis: prophylactic immunisation followed by challenge with H felis or H pylori can induce a more severe gastritis in mice than seen with infection alone. The aim of this study was to investigate the relationship between immunity to Helicobacter infection and post-immunisation gastritis.(1) C57BL/6 mice were prophylactically immunised before challenge with either H felis or H pylori. Histopathology and colonisation were assessed one month post-challenge. (2) C57BL/6 mice were prophylactically immunised against H felis infection and gastritis assessed up to 18 months post-challenge.Prophylactic immunisation induced a reduction in bacterial colonisation following H felis challenge which was associated with increased severity of active gastritis with neutrophil infiltration and atrophy. However, immunised mice challenged with H pylori SS1 had little evidence of pathology. Long term follow up showed that post-immunisation gastritis was evident at three months. However, from six months onwards, although immunised/challenged mice still developed gastritis, there was no significant difference between inflammation in these mice and infected controls. Post-immunisation gastritis was not associated with the serum antibody response. Immunisation prevented the formation of secondary lymphoid aggregates in the gastric tissue.The H felis mouse model of post-immunisation gastritis is the most extreme example of this type of pathology. We have shown in this model that post-immunisation gastritis is a transient event which does not produce long term exacerbation of pathology.
Connective tissue growth factor expression is regulated by histamine in lung fibroblasts: Potential role of histamine in airway remodeling
Authors: Steffen Kunzmann, Carsten Schmidt-Weber, Jean-Marc Zingg, Angelo Azzi, Boris W. Kramer, Kurt Blaser, Cezmi A. Akdis, Christian P. Speer
Journal: Journal of Allergy and Clinical Immunology (2007)
Avian B-Cell Development: Generation of an Immunoglobulin Repertoire by Gene Conversion
Authors: W T McCormack, L W Tjoelker, C B Thompson
Journal: Annual Review of Immunology (1991)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Gene Variants Associated With Deep Vein Thrombosis
Authors: Irene D. Bezemer
Journal: JAMA (2008)

The genetic causes of deep vein thrombosis (DVT) are not fully understood.To identify single-nucleotide polymorphisms (SNPs) associated with DVT.We used 3 case-control studies of first DVT. A total of 19 682 gene-centric SNPs were genotyped in 443 cases and 453 controls from the Leiden Thrombophilia Study (LETS, 1988-1992). Twelve hundred six SNPs associated with DVT were reinvestigated in the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis study (MEGA-1, 1999-2004) in a subset of 1398 cases and 1757 controls. Nine SNPs associated with DVT in both LETS and MEGA-1 were investigated a third time in 1314 cases and 2877 controls from MEGA-2, a second subset of MEGA. Additional SNPs close to one SNP in CYP4V2 were genotyped in LETS and MEGA-1.Odds ratios (ORs) for DVT were estimated by logistic regression. False discovery rates served to investigate the effect of multiple hypothesis testing.Of 9 SNPs genotyped in MEGA-2, 3 were strongly associated with DVT (P < .05; false discovery rate < or =.10): rs13146272 in CYP4V2 (risk allele frequency, 0.64), rs2227589 in SERPINC1 (risk allele frequency, 0.10), and rs1613662 in GP6 (risk allele frequency, 0.84). The OR for DVT per risk allele was 1.24 (95% confidence interval [95%CI], 1.11-1.37) for rs13146272, 1.29 (95% CI, 1.10-1.49) for rs2227589, and 1.15 (95% CI, 1.01-1.30) for rs1613662. In the region of CYP4V2, we identified 4 additional SNPs (in CYP4V2, KLKB1, and F11) that were also associated with both DVT (highest OR per risk allele, 1.39; 95% CI, 1.11-1.74) and coagulation factor XI level (highest increase per risk allele, 8%; 95% CI, 5%-11%).We identified SNPs in several genes that were associated with DVT. We also found SNPs in the region around the SNP in CYP4V2 (rs13146272) that were associated with both DVT and factor XI levels. These results show that common genetic variation plays an important role in determining thrombotic risk.