tbuckley/cabot-search huggingface dataset:
Identification of Alternative Splicing Markers for Breast Cancer
Authors: Julian P. Venables, Roscoe Klinck, Anne Bramard, Lyna Inkel, Geneviève Dufresne-Martin, ChuShin Koh, Julien Gervais-Bird, Elvy Lapointe, Ulrike Froehlich, Mathieu Durand, Daniel Gendron, Jean-Philippe Brosseau, Philippe Thibault, Jean-Francois Lucier, Karine Tremblay, Panagiotis Prinos, Raymund J. Wellinger, Benoit Chabot, Claudine Rancourt, Sherif Abou Elela
Journal: Cancer Research (2008)

Abstract Breast cancer is the most common cause of cancer death among women under age 50 years, so it is imperative to identify molecular markers to improve diagnosis and prognosis of this disease. Here, we present a new approach for the identification of breast cancer markers that does not measure gene expression but instead uses the ratio of alternatively spliced mRNAs as its indicator. Using a high-throughput reverse transcription-PCR–based system for splicing annotation, we monitored the alternative splicing profiles of 600 cancer-associated genes in a panel of 21 normal and 26 cancerous breast tissues. We validated 41 alternative splicing events that significantly differed in breast tumors relative to normal breast tissues. Most cancer-specific changes in splicing that disrupt known protein domains support an increase in cell proliferation or survival consistent with a functional role for alternative splicing in cancer. In a blind screen, a classifier based on the 12 best cancer-associated splicing events correctly identified cancer tissues with 96% accuracy. Moreover, a subset of these alternative splicing events could order tissues according to histopathologic grade, and 5 markers were validated in a further blind set of 19 grade 1 and 19 grade 3 tumor samples. These results provide a simple alternative for the classification of normal and cancerous breast tumor tissues and underscore the putative role of alternative splicing in the biology of cancer. [Cancer Res 2008;68(22):9525–31]
Functional Analysis of PIK3CA Gene Mutations in Human Colorectal Cancer
Authors: Tsuneo Ikenoue, Fumihiko Kanai, Yohko Hikiba, Toshiyuki Obata, Yasuo Tanaka, Jun Imamura, Miki Ohta, Amarsanaa Jazag, Bayasi Guleng, Keisuke Tateishi, Yoshinari Asaoka, Masayuki Matsumura, Takao Kawabe, Masao Omata
Journal: Cancer Research (2005)

Abstract Mutations in the PIK3CA gene, which encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been reported in human cancers, including colorectal cancer. Most of the mutations cluster at hotspots within the helical and kinase domains. Whereas H1047R, one of the hotspot mutants, is reported to have elevated lipid kinase activity, the functional consequences of other mutations have not been examined. In this study, we examined the effects of colon cancer–associated PIK3CA mutations on the lipid kinase activity in vitro, activation of the downstream targets Akt and p70S6K in vivo and NIH 3T3-transforming ability. Of eight mutations examined, all showed increased lipid kinase activity compared with wild-type p110α. All the mutants strongly activated Akt and p70S6K compared with wild-type p110α as determined by immunoblotting using phospho-specific antibodies. These mutants also induced morphologic changes, loss of contact inhibition, and anchorage-independent growth of NIH 3T3 cells. The hotspot mutations examined in this study, E542K, E545K, and H1047R, all had high enzymatic and transforming activities. These results show that almost all the colon cancer–associated PIK3CA mutations are functionally active so that they are likely to be involved in carcinogenesis.
Epstein—Barr virus association in classical Hodgkin's disease provides survival advantage to patients and correlates with higher expression of proliferation markers in Reed—Sternberg cells
Authors: K.N. Naresh, J. Johnson, V. Srinivas, C.S. Soman, T. Saikia, S.H. Advani, R.A. Badwe, K.A. Dinshaw, M. Muckaden, I. Magrath, K. Bhatia
Journal: Annals of Oncology (2000)
Immune System May Benefit From the Ability to Laugh
Authors: J. Ziegler
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Immune System May Benefit From the Ability to Laugh Get access Jan Ziegler Jan Ziegler Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 5, 1 March 1995, Pages 342–343, https://doi.org/10.1093/jnci/87.5.342 Published: 01 March 1995
Bias from requiring explicit consent from all participants in observational research: prospective, population based study
Authors: Rustam Al-Shahi, Céline Vousden, Charles Warlow
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate the differences between adults who consent to participate in observational research, and those who do not. <b>Design</b> Prospective, population based cohort study. <b>Setting</b> Primary and secondary care throughout Scotland. <b>Participants</b> 187 adults (aged ≥16 years) resident in Scotland at the time of their first diagnosis of a brain arteriovenous malformation in 1999-2002. <b>Intervention</b> Postal consent form sent via participants9 general practitioner. <b>Main outcome measures</b> Differences between consenters and non-consenters in demographic and clinical features at first presentation, and outcome during follow-up. <b>Results</b> 111 adults (59%) consented to participate in the study. These consenters were not significantly different from non-consenters in age, sex, or socioeconomic status at first presentation. However, consenters were significantly more likely than non-consenters to present alive and independent, and with a seizure. During follow-up, consenters were significantly more likely to receive interventional treatment. Although consenters9 survival was significantly better, they were more likely to have a seizure during follow-up. Presentation with intracranial haemorrhage conferred a higher risk of subsequent haemorrhage when the whole cohort was analysed, but not when it was restricted to consenters. <b>Conclusions</b> We have found differences between adults who consent to participate in observational records-based research and those who do not, or cannot, consent. Blanket requirements for explicit consent for the use of individuals9 identifiable data can bias disease registers, epidemiological studies, and health services research.
Optimal Dose of Candesartan for Renoprotection in Type 2 Diabetic Patients With Nephropathy
Authors: Kasper Rossing, Per K. Christensen, Birgitte V. Hansen, Bendix Carstensen, Hans-Henrik Parving
Journal: Diabetes Care (2003)

OBJECTIVE—We evaluated the optimal dose of the angiotensin II receptor antagonist candesartan cilexetil for renoprotection as reflected by short-term changes in albuminuria in hypertensive type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS—A total of 23 hypertensive patients with type 2 diabetes and nephropathy were enrolled in this double-blind randomized cross-over trial with four treatment periods, each lasting 2 months. Each patient received placebo and candesartan: 8, 16, and 32 mg daily in random order. Antihypertensive medication was discontinued before enrollment, except for long-acting furosemide, which all patients received throughout the study in median (range) doses of 40 (30–160) mg daily. End points were albuminuria (turbidimetry), 24-h blood pressure (BP) (Takeda-TM2420), and glomerular filtration rate (GFR) (51Cr-labeled EDTA plasma clearance technique). RESULTS—Values obtained during placebo treatment: albuminuria [geometric mean (95% CI)] 700 (486–1,007) mg/24-h, 24-h BP (mean ± SE) 147 ± 4/78 ± 2 mmHg, and GFR 84 ± 6 ml/min/1.73 m2. All three doses of candesartan significantly reduced albuminuria and 24-h BP compared with placebo. Mean (95% CI) reductions in albuminuria were 33% (21–43), 59% (52–65), and 52% (44–59) with increasing doses of candesartan. Albuminuria was reduced significantly more by the two highest doses than by the lowest dose (P &amp;lt; 0.01); 24-h systolic BP was reduced by 9 (2–16), 9 (2–16), and 13 (6–20) mmHg and 24-h diastolic BP was reduced by 5 (2–8), 4 (1–7), and 6 (3–9) mmHg with increasing doses of candesartan. There were no significant differences in the reductions in BP between the three doses. GFR was decreased by ∼6 ml/min/1.73 m2 by all three doses of candesartan (P &amp;lt; 0.05 versus placebo). CONCLUSIONS—The optimal dose of candesartan is 16 mg daily for renoprotection, as reflected by short-term reduction in albuminuria, in hypertensive type 2 diabetic patients with nephropathy.
Retrograde Invasion of the Bundle Branches Producing Aberration of the QRS Complex During Supraventricular Tachycardia Studied by Programmed Electrical Stimulation
Authors: ROWORTHA A. J. SPURRELL, DENNIS M. KRIKLER, EDGAR SOWTON
Journal: Circulation (1974)

Four patients with paroxysmal supraventricular tachycardia have been studied using programmed electrical stimulation of the heart and intracardiac recordings. One patient had an atrioventricular (A-V) junctional tachycardia, possibly due to a rapidly discharging protected ectopic focus, and three patients had anomalous atrioventricular connections. The ECG recordings in all four patients showed a bundle branch block pattern during tachycardia, and normal intraventricular conduction could be produced by suitably timed right ventricular premature beats. The cycle length of the tachycardia was shorter with normal intraventricular conduction than in the presence of a bundle branch block pattern in two patients. Evidence is presented indicating that the bundle branch block during tachycardia was likely to be due to concealed retrograde conduction of the appropriate bundle branch, and in the presence of an anomalous bypass, the cycle length of the tachycardia depended on the anatomical relationship of the anomalous bypass to the blocked bundle branch.
A Randomized Trial of Dietary Sodium Restriction in CKD
Authors: Emma J. McMahon, Judith D. Bauer, Carmel M. Hawley, Nicole M. Isbel, Michael Stowasser, David W. Johnson, Katrina L. Campbell
Journal: Journal of the American Society of Nephrology (2013)

There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3–4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.
An HLA-DR5 homozygous cell line expresses two DS (I-A-like) molecules.
Authors: R W Karr, C C Kannapell, R J Zangara, S M Goyert, J Silver, B D Schwartz
Journal: The Journal of Experimental Medicine (1983)

Previous studies have indicated that LLA-DR homozygous cell lines express two DR molecules but only a single DS (I-A-like) molecule. This report demonstrates that an HLA-DR5 homozygous cell line expresses at least two distinct DS molecules. These two DS molecules are formed by the association of a single DS alpha chain with either of two DS beta chains. Four distinct Ia molecules have now been identified from this DR5 homozygous cell line.
Familial adenomatous polyposis patients without an identified APC germline mutation have a severe phenotype
Authors: M L Bisgaard
Journal: Gut (2004)

Development of more than 100 colorectal adenomas is diagnostic of the dominantly inherited autosomal disease familial adenomatous polyposis (FAP). Germline mutations can be identified in the adenomatous polyposis coli (APC) gene in approximately 80% of patients. The APC protein comprises several regions and domains for interaction with other proteins, and specific clinical manifestations are associated with the mutation assignment to one of these regions or domains.The phenotype in patients without an identified causative APC mutation was compared with the phenotype in patients with a known APC mutation and with the phenotypes characteristic of patients with mutations in specific APC regions and domains.Data on 121 FAP probands and 149 call up patients from 70 different families were extracted from the Danish Polyposis register.Differences in 16 clinical manifestations were analysed according to the patient's mutational status. Two sided independent t sample test, two sided chi(2) test, and odds ratios were calculated.Patients without identified APC mutations had a unique and severe phenotype, which was roughly described as: young age at diagnosis and subsequent death in spite of development of few colorectal adenomas; low risk of involvement of the upper gastrointestinal tract, as reflected by a low mean Spigelman stage, and a low risk of fundic gland polyposis. Finally, they had significantly fewer affected family members, although they do not themselves more often represent an isolated case.The severe phenotype should be considered when counselling FAP families in which attenuated FAP is excluded and in which a causative APC mutation has not been identified.
Quantitative studies on the precursors of cytotoxic lymphocytes. VI. Second signal requirements of specifically activated precursors isolated 12 h after stimulation.
Authors: M E Lalande, M J McCutcheon, R G Miller
Journal: The Journal of Experimental Medicine (1980)

It is shown that, in a mixed lymphocyte reaction, the production of cytotoxic T lymphocytes (CL) from cytotoxic T lymphocyte precursors (CLP) requires two signals which are separated time. Using a flow cytometer-cell sorter and a vital, fluorescent DNA stain, Hoechst 3342, CLP specific for the stimulator cells can be separated from other CLP and from stimulator cells 12 h after initiation of mixed lymphocyte cultures. These CLP are in a state of partial activation and can produce CL in the absence of stimulator cells if a second signal in the form of a concanavalin A-induced spleen cell supernate factor is added. Specific CL are also generated when the partially activated CLP are cultured with both nude spleen cells and stimulator cells. In this case it appears that an interaction between the stimulator cells and the nude spleen cells leads to production of the second signal.
LEO1 Is Regulated by PRL-3 and Mediates Its Oncogenic Properties in Acute Myelogenous Leukemia
Authors: Phyllis S.Y. Chong, Jianbiao Zhou, Lip-Lee Cheong, Shaw-Cheng Liu, Jingru Qian, Tiannan Guo, Siu Kwan Sze, Qi Zeng, Wee Joo Chng
Journal: Cancer Research (2014)

PRL-3, an oncogenic dual-specificity phosphatase, is overexpressed in 50% of acute myelogenous leukemia (AML) and associated with poor survival. We found that stable expression of PRL-3 confers cytokine independence and growth advantage of AML cells. However, how PRL-3 mediates these functions in AML is not known. To comprehensively screen for PRL3-regulated proteins in AML, we performed SILAC-based quantitative proteomics analysis and discovered 398 significantly perturbed proteins after PRL-3 overexpression. We show that Leo1, a component of RNA polymerase II-associated factor (PAF) complex, is a novel and important mediator of PRL-3 oncogenic activities in AML. We described a novel mechanism where elevated PRL-3 protein increases JMJD2C histone demethylase occupancy on Leo1 promoter, thereby reducing the H3K9me3 repressive signals and promoting Leo1 gene expression. Furthermore, PRL-3 and Leo1 levels were positively associated in AML patient samples (N=24; P<0.01). On the other hand, inhibition of Leo1 reverses PRL-3 oncogenic phenotypes in AML. Loss of Leo1 leads to destabilization of the PAF complex and downregulation of SOX2 and SOX4, potent oncogenes in myeloid transformation. In conclusion, we identify an important and novel mechanism by which PRL-3 mediates its oncogenic function in AML.
New antithrombin‐based anticoagulants
Authors: Umesh R. Desai
Journal: Medicinal Research Reviews (2003)

Clinically used anticoagulants are inhibitors of enzymes involved in the coagulation pathway, primarily thrombin and factor Xa. These agents can be either direct or indirect inhibitors of clotting enzymes. Heparin-based anticoagulants are indirect inhibitors that enhance the proteinase inhibitory activity of a natural anticoagulant, antithrombin. Despite its phenomenal success, current anticoagulation therapy suffers from the risk of serious bleeding. The need for safer and more effective antithrombotic agents clearly exists. The past decade has seen enormous effort directed toward discovering and/or designing new molecules with anticoagulant activity. These new molecules can be classified into (a). antithrombin and its mutants, (b). natural polysaccharides, (c). synthetic modified heparins and heparin-mimics, (d). synthetic oligosaccharides, and (e). synthetic non-sugar antithrombin activators. This review focuses on these efforts in designing or discovering new molecules that act through the antithrombin pathway of anticoagulation.
Preoperative Combined Nested Reverse Transcriptase Polymerase Chain Reaction for Prostate-Specific Antigen and Prostate-Specific Membrane Antigen Does Not Correlate With Pathologic Stage or Biochemical Failure in Patients With Localized Prostate Cancer Undergoing Radical Prostatectomy
Authors: John Thomas, Manjula Gupta, Ying Grasso, Chandana A. Reddy, Warren D. Heston, Craig Zippe, Robert Dreicer, Patrick A. Kupelian, Jennifer Brainard, Howard S. Levin, Eric A. Klein
Journal: Journal of Clinical Oncology (2002)

We report a prospective study examining the ability of preoperative nested reverse transcriptase polymerase chain reaction (RT-PCR) for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) to predict pathologic stage and biochemical recurrence in patients with clinically localized prostate cancer treated with radical prostatectomy.One hundred forty-one patients were entered onto the study. Preoperative evaluation included clinical T stage, serum PSA, biopsy Gleason score, and serum RT-PCR for PSA/PSM. Univariate and multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional hazards modeling were used to identify predictors of pathologic stage and biochemical failure.Seventy-three patients (51.8%) were RT-PCR positive for PSA, PSM, or both. In the multivariate logistic regression model, only initial PSA was an independent predictor of pathologic stage as defined by organ-confined disease (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.00 to 1.13; P =.026) or organ-/specimen-confined disease (OR, 1.09; 95% CI, 1.02 to 1.16; P =.009). Overall Kaplan-Meier biochemical relapse-free survival (bRFS) was 85% at 59 months. Multivariate analysis of predictors for bRFS with the Cox proportional hazards model indicated that only initial PSA (OR, 1.05; 95% CI, 1.02 to 1.09; P =.004) and biopsy Gleason score (OR, 3.57; 95% CI, 1.37 to 9.58; P =.009) were independent predictors of biochemical failure. RT-PCR status did not predict pathologic stage or biochemical failure. Repeat analysis excluding 27 patients who received preoperative androgen-deprivation therapy did not change the results.Combined nested RT-PCR for PSA and PSM is not an independent predictor of pathologic stage or biochemical failure in patients with localized prostate cancer undergoing radical prostatectomy. This assay has no clinical utility in this patient population.
A–Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance—part 12
Authors: K Currell, A Syed, C E Dziedzic, D S King, L L Spriet, J Collins, L M Castell, S J Stear, L M Burke
Journal: British Journal of Sports Medicine (2010)

This part of our A–Z series contains five articles on a wide variety of topics. For the sake of continuity, some topics in the alphabetical listing have been moved further down: curcumin, which will appear collectively with flavonoids; docosahexanoic acid and eicosapentanoic acid, which will now come under the umbrella of fatty acids. The compounds covered in part 12 range considerably in their composition and their physiological roles in the body. However, they do share some common characteristics, which might be seen as a generic description of most of the supplements marketed to athletes. Each has a mechanism by which it is proposed that supplementation might improve sports performance, based on the enhancement of an existing biochemical or hormonal pathway that is considered limiting. The marketing credibility of each of these supplements, and others, is boosted from time to time by anecdotal reports of use by a successful athlete or popularity within a certain sporting population. For example, dehydroepiandrosterone achieved notoriety in sporting circles when American baseball player, Mark McGwire, provided testimonials regarding its use during the 1998 season in which he broke the league record for hitting home runs. Alternatively, dimethylglycine has enjoyed the mystique among Western athletes of being used by athletes from Eastern Bloc countries. However, the most important characteristic is that each product has received only minor attention from sports scientists, in terms of involvement in well-conducted, randomised, controlled trials, specific to sport.

### K Currell, A Syed

Cysteine is a non-essential amino acid and, together with glycine and glutamate, is an important precursor of the tripeptide glutathione. Glycine and glutamate are readily available within the body and it is thought that the limiting step in the synthesis of glutathione is the availability of cysteine.1 Glutathione is one of the key antioxidants within the body2 and is an essential …
Risk factors for metastatic osteoarticular infections after a long follow-up of patients with Staphylococcus aureus bacteraemia
Authors: A. Lalueza, A. Morales-Cartagena, F. Chaves, R. San Juan, J. Laureiro, J. Lora-Tamayo, F. López-Medrano, M.Á. Orellana, J.M. Aguado
Journal: Clinical Microbiology and Infection (2015)