tbuckley/cabot-search huggingface dataset:
Lysoplasmenylethanolamine accumulation in ischemic/reperfused isolated fatty acid-perfused hearts.
Authors: N J Davies, R Schulz, P M Olley, K D Strynadka, D L Panas, G D Lopaschuk
Journal: Circulation Research (1992)

Lysophospholipid accumulation has been implicated in the pathogenesis of irreversible injury during myocardial ischemia and reperfusion. Plasmalogens (phospholipids with a vinyl-ether bond in the sn-1 position) account for more than 50% of total myocardial sarcolemmal and sarcoplasmic reticulum phospholipids. Accumulation of plasmalogen choline and ethanolamine lysophospholipids (lysoplasmenylcholine and lysoplasmenylethanolamine) or the effects of exogenous fatty acids on lysoplasmalogen accumulation during ischemia and reperfusion have not been examined. Isolated working rat hearts perfused with buffer containing either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate were subjected to aerobic, ischemic, or ischemia/reperfusion protocols. Levels of lysoplasmenylcholine and lysoplasmenylethanolamine were quantified using a two-stage high-performance liquid chromatographic technique. In hearts perfused with glucose alone, no significant differences in levels of lysoplasmenylcholine or lysoplasmenylethanolamine were seen during ischemia or reperfusion. In fatty acid-perfused hearts, however, significant accumulation of lysoplasmenylethanolamine occurred during reperfusion but not during ischemia (723 +/- 112, 734 +/- 83, and 1,394 +/- 193 nmol/g dry wt for aerobic, ischemic, and ischemic/reperfused hearts, respectively; p less than 0.05 for ischemic/reperfused hearts versus aerobic or ischemic hearts). Lysoplasmenylcholine levels after ischemia and reperfusion did not differ significantly from aerobic values, regardless of whether fatty acids were present or absent from the perfusate. Aerobic and ischemic/reperfused rabbit hearts, in the presence of fatty acid, showed a similar profile in their lysoplasmalogen content. We conclude that differential lysoplasmenylethanolamine accumulation occurs during myocardial reperfusion when exogenous fatty acid concentrations are high. This may reflect the selective action of fatty acid intermediates on the metabolism of lysoplasmenylethanolamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase I Study of STX 64 (667 Coumate) in Breast Cancer Patients: The First Study of a Steroid Sulfatase Inhibitor
Authors: Susannah J. Stanway, Atul Purohit, L.W. Lawrence Woo, Saulat Sufi, David Vigushin, Rebecca Ward, Richard H. Wilson, Frank Z. Stanczyk, Nicola Dobbs, Elena Kulinskaya, Moira Elliott, Barry V.L. Potter, Michael J. Reed, R. Charles Coombes
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Inhibition of steroid sulfatase (STS), the enzyme responsible for the hydrolysis of steroid sulfates, represents a potential novel treatment for postmenopausal women with hormone-dependent breast cancer. Estrone and DHEA are formed by this sulfatase pathway and can be converted to steroids (estradiol and androstenediol, respectively), which have potent estrogenic properties. Experimental Design: STX64 (667 Coumate), a tricylic coumarin-based sulfamate that irreversibly inhibits STS activity, was selected for entry into the first phase I trial of a STS inhibitor in postmenopausal women with breast cancer. STX64 was administered orally (nine patients at 5 mg and five patients at 20 mg) as an initial dose followed 1 week later by 3 × 2 weekly cycles, with each cycle comprising daily dosing for 5 days followed by 9 days off treatment. Blood and tumor tissue samples were collected for the assessment of STS activity and serum was obtained for steroid hormone measurements before and after treatment. Results: The median inhibition of STS activity by STX64 was 98% in peripheral blood lymphocytes (PBL) and 99% in breast tumor tissue at the end of the 5-day dosing period. As expected, serum concentrations of estrone, estradiol, androstenediol, and DHEA all decreased significantly from pretreatment levels. Unexpectedly, androstenedione and testosterone concentrations also decreased. Four patients, all of whom had previously progressed on aromatase inhibitors, showed evidence of stable disease for 2.75 to 7 months. The drug was well tolerated with only minor drug-related adverse events recorded. Conclusion: STX64 is a potent, well-tolerated STS inhibitor. It inhibits STS activity in PBLs and tumor tissues and causes significant decreases in serum concentrations of steroids with estrogenic properties.
Chromatin Remodeling and Transcriptional Regulation
Authors: R. X. Luo, D. C. Dean
Journal: JNCI Journal of the National Cancer Institute (1999)

Extensive studies in the past few years have begun to demonstrate that chromosome structure plays a critical role in transcriptional regulation. Two highly conserved mechanisms for altering chromosome structure have been identified: 1) post-translational modification of histones and 2) adenosine triphosphate (ATP)-dependent chromosome remodeling. Acetylation of histone lysine residues has been known for three decades to be associated with transcriptional activation. Recent discoveries, however, show that a number of transcriptional regulators are histone acetylases or histone deacetylases. Specific DNA-binding transcription factors recruit histone acetylases and deacetylases to promoters to activate or repress transcription. These results strongly support the notion that histone acetylation and deacetylation play an important role in transcriptional regulation. Recent findings have also provided insight into the molecular mechanisms by which ATP-dependent chromosome-remodeling activities participate in transcriptional regulation. Furthermore, some ATP-dependent chromosome-remodeling activities have been shown to complex with histone deacetylases. In the complexes studied to date, the ATP-dependent chromosome-remodeling activity enhances the histone deacetylase activity. Therefore, the two mechanisms appear to work in concert to achieve precise control of transcription. Disruption of chromosome remodeling has been linked to a number of diseases, and a complete understanding of the complex chromosome-remodeling machinery may lead to the development of new therapies.
Stromal Cell-Derived Factor-1 as a Chemoattractant for Follicular Center Lymphoma B Cells
Authors: A. Corcione, L. Ottonello, G. Tortolina, P. Facchetti, I. Airoldi, R. Guglielmino, P. Dadati, M. Truini, S. Sozzani, F. Dallegri, V. Pistoia
Journal: JNCI Journal of the National Cancer Institute (2000)

Background: Follicular center lymphoma displays widespread lymph node involvement at diagnosis. The chemoattractants that control the locomotion of follicular center lymphoma B cells have not been established. Stromal cell-derived factor-1 (SDF-1) is a CXC-class chemokine that enhances the migration of normal human B cells and is expressed in peripheral lymphoid tissues. Here we have investigated 1) whether SDF-1 stimulates the in vitro locomotion of follicular center lymphoma B cells and of their presumed normal counterparts (i.e., germinal center B cells) and 2) whether the same cells express SDF-1 transcripts. Methods: B cells were purified by immunomagnetic bead manipulation. Messenger RNA was detected by reverse transcription–polymerase chain reaction. Migration was assessed by the filter and collagen invasion assays. All P values were two sided. Results: Follicular center lymphoma B lymphocytes showed a statistically significant migratory response to 300 ng/mL SDF-1, both in the filter and in the collagen assays (P = .002 for each). Such response was mediated by the SDF-1 receptor, CXCR4. CD40 monoclonal antibody (MAb) and tonsillar germinal center B cells treated with CD40 MAb and recombinant interleukin 4, but not freshly isolated, migrated statistically significantly faster in the presence than in the absence of SDF-1 (P = .002 in both filter and collagen assays). Freshly isolated follicular center lymphoma and germinal center B cells expressed SDF-1 transcripts. Conclusions: This study shows that SDF-1 substantially enhances the migration of follicular center lymphoma B cells but not the migration of freshly purified germinal center B cells. This difference may be related to the extended survival of follicular center lymphoma versus germinal center B cells. SDF-1 produced in follicular center lymphoma lymph nodes may play a role in the local dissemination of tumor cells.
Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12
Authors: M. Gnant, B. Mlineritsch, H. Stoeger, G. Luschin-Ebengreuth, M. Knauer, M. Moik, R. Jakesz, M. Seifert, S. Taucher, V. Bjelic-Radisic, M. Balic, H. Eidtmann, W. Eiermann, G. Steger, W. Kwasny, P. Dubsky, U. Selim, F. Fitzal, G. Hochreiner, V. Wette, P. Sevelda, F. Ploner, R. Bartsch, C. Fesl, R. Greil
Journal: Annals of Oncology (2014)
Adoptive suppression of granuloma formation.
Authors: D G Colley
Journal: The Journal of Experimental Medicine (1976)

Anti-egg granulomas formed in mice with chronic S. mansoni infection are smaller than those formed early (8 wk) after infection. Passive transfer of serum from mice with chronic infections to recipient mice with developing (6 wk) infections did not affect hepatic granuloma size at 8 wk of infection. In contrast, either spleen cells or lymph node cells from mice with chronic infections strongly suppressed the granulomatous process in recipient mice. Spleen cells, but not lymph node cells, of early-(7 wk) infected mice exhibited some ability to diminish granuloma formation in recipients. It appeared that the use of two sequential, weekly passive transfers of spleen or lymph node cells from chronic mice was even more effective in this suppressive capacity than a single transfer.
Self-report scales/checklists for the measurement of concussion symptoms: a systematic review
Authors: S Alla, S J Sullivan, L Hale, P McCrory
Journal: British Journal of Sports Medicine (2009)

Objective: To identify self-reported sport concussion symptom scales and to describe the psychometric properties of these identified scales. Design: Systematic review. Intervention: PubMed, Medline, CINAHL, Scopus, Web of Science, Sport Discus, PsycINFO and AMED were searched from their establishment until December 2008. The medical subject heading terms “brain concussion”, “signs or symptoms” and “athletic injuries”. The search was limited to articles published in English. An additional search of the reference lists of the retrieved articles was conducted. Only full-text articles were considered for this study and these were retrieved to determine whether they met the inclusion criteria. Results: The initial search resulted in 421 articles, which were reduced to 290 articles after removing duplicates. The hand search resulted in 17 articles, thus giving a total of 307 articles. Full text was available for 295 articles of which 60 met the criteria for inclusion. The excluded 235 articles were case reports, reviews and guidelines on concussion management or studies that had not used a symptom scale or checklist. Conclusions: Six core scales were identified with a broad range of symptom items but with limited information on their psychometric properties. There were numerous derivative scales reported, most of which have not been methodically developed or subjected to scientific scrutiny. Despite this, they do make a contribution to the detection, assessment and return to play decisions but there is a need for the clinical user to be aware that many of these scales have “evolved” rather than being scientifically developed.
Phenotypic differences in familial adenomatous polyposis based on APC gene mutation status
Authors: K Heinimann, B Müllhaupt, W Weber, M Attenhofer, R J Scott, M Fried, S Martinoli, Hj Müller, Z Dobbie
Journal: Gut (1998)

Background —Familial adenomatous polyposis (FAP) is a clinically well defined hereditary disease caused by germline mutations within the adenomatous polyposis coli (APC) gene. Although several techniques are applied in the mutation analysis of FAP kindreds about 20–50% of cases remain unclear, with no APC mutation identified (APC negative). Aims —To delineate phenotypic differences between APC positive and APC negative patients with respect to colonic and extracolonic disease in order to determine whether additional mechanisms are involved in the pathogenesis of FAP. Methods —The entire coding region of the APC gene was analysed using single stranded conformation polymorphism and protein truncation tests in 50 Swiss FAP families with a total of 161 affected individuals. Differences in phenotypic manifestation were statistically evaluated by Student’s t test, Fisher’s exact test, and χ 2 test. Results —Thirty six families (72%) were APC positive. Statistically significant differences between APC positive and APC negative groups were found for the mean age at diagnosis of colonic polyposis (35.2 versus 45.3 years, respectively) and for the occurrence of stomach polyps (14 patients, all APC positive). Additionally, APC negative patients displayed lower polyp numbers at diagnosis and less extracolonic manifestations. Conclusions— FAP kindreds without detected APC gene mutations present with a notably milder disease phenotype compared with APC positive families, suggesting that different genetic factors might be involved.
An Avoidable Cause of False Home Glucose Measurements
Authors: David E. Steward, Romesh Khardori
Journal: Diabetes Care (2001)

In patients with type 2 diabetes, tight control of blood glucose reduces complications and improves outcomes. As a result, increasing numbers of elderly patients with type 2 diabetes are being advised to measure blood glucose at home. For these elderly patients, who are at risk to have impaired cognition, vision, and dexterity, it is especially important that their home glucose meters provide accurate, reliable results and are simple to operate. We report a case of an elderly patient who suffered falsely elevated home glucose measurements for an interesting and avoidable cause.

An 89-year-old man with type 2 diabetes had been managed for many years with low daily doses of insulin. After an adjustment of …
Treatment of the Amblyopic Eye
Authors: W. H. Summerskill
Journal: BMJ (1936)

The creatine and creatinine metabolism was not altered by the use of prostigmin: average daily excretion of creatine (Case No. 2) was 0.02 gram per day before the injections and 0.025 gram per day after the injections.The creatinine excretion was 1 gram per day before the injections, and 0.9 gram per day after the injections.The diet was the same during the observations, and these findings agree with those of Cooke and Passmore.The injections produced no systemic disturbance and caused no inconvenience to the patients, and the psycho- logical improvement in their outlook was very gratifying.The two cases are being kept under observation, and it is hoped that favourable reports of their progress will be given at some future date.These observations have been made while holding the appointment of house-physician to Professor A. Ramsbottom in the Royal Infirmary, Manchester.I am indebted to Professor Ramsbottom and Mr. Geoffrey Jefferson
ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)
Authors: F. Cardoso, A. Costa, L. Norton, E. Senkus, M. Aapro, F. André, C.H. Barrios, J. Bergh, L. Biganzoli, K.L. Blackwell, M.J. Cardoso, T. Cufer, N. El Saghir, L. Fallowfield, D. Fenech, P. Francis, K. Gelmon, S.H. Giordano, J. Gligorov, A. Goldhirsch, N. Harbeck, N. Houssami, C. Hudis, B. Kaufman, I. Krop, S. Kyriakides, U.N. Lin, M. Mayer, S.D. Merjaver, E.B. Nordström, O. Pagani, A. Partridge, F. Penault-Llorca, M.J. Piccart, H. Rugo, G. Sledge, C. Thomssen, L. van't Veer, D. Vorobiof, C. Vrieling, N. West, B. Xu, E. Winer
Journal: Annals of Oncology (2014)

Advanced breast cancer (ABC) is a treatable but still generally incurable disease. The goals of care are to optimize both length and quality of life. Due to continuous research, several advances have been made, particularly for the human epidermal growth factor receptor 2 (HER-2)-positive and for luminal-like subtypes. Notwithstanding these advances, median overall survival of patients with ABC is still only 2–3 years, although the range is wide [1–5], and survival may be longer for patients treated in specialized institutions [6].
Dietary Linoleic Acid and Risk of Coronary Heart Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies
Authors: Maryam S. Farvid, Ming Ding, An Pan, Qi Sun, Stephanie E. Chiuve, Lyn M. Steffen, Walter C. Willett, Frank B. Hu
Journal: Circulation (2014)

Previous studies on intake of linoleic acid (LA), the predominant n-6 fatty acid, and coronary heart disease (CHD) risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of dietary LA intake and CHD risk.
Management Strategies for Asymptomatic Carotid Stenosis
Authors: Gowri Raman, Denish Moorthy, Nira Hadar, Issa J. Dahabreh, Thomas F. O'Donnell, David E. Thaler, Edward Feldmann, Joseph Lau, Georgios D. Kitsios
Journal: Annals of Internal Medicine (2013)

Background: Adults with asymptomatic carotid artery stenosis are at increased risk for ipsilateral carotid territory ischemic stroke. Purpose: To examine comparative evidence on management strategies for asymptomatic carotid stenosis and the incidence of ipsilateral stroke with medical therapy alone. Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration documents, and review of references through 31 December 2012. Study Selection: Randomized, controlled trials (RCTs) and prospective or retrospective nonrandomized, comparative studies of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting (CAS) plus medical therapy for adults with asymptomatic carotid stenosis, as well as single-group prospective cohort studies of medical therapy, were reviewed. Data Extraction: Two investigators extracted information on study and population characteristics, results, and risk of bias. Data Synthesis: Forty-seven studies in 56 publications were eligible. The RCTs comparing CAS and CEA were clinically heterogeneous; 1 RCT reported more but not statistically significant ipsilateral stroke events (including any periprocedural stroke) in CAS compared with CEA, whereas another RCT, in a population at high surgical risk for CEA, did not. Three RCTs showed that CEA reduced the risk for ipsilateral stroke (including any periprocedural stroke) compared with medical therapy alone, but these results may no longer be applicable to contemporary clinical practice. No RCT compared CAS versus medical therapy alone. The summary incidence of ipsilateral stroke across 26 cohorts receiving medical therapy alone was 1.68% per year. Limitations: Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best-available medical therapy. Conclusion: Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy. Primary Funding Source: Agency for Healthcare Research and Quality.
Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD
Authors: Edaire Cheng, Xi Zhang, Xiaofang Huo, Chunhua Yu, Qiuyang Zhang, David H Wang, Stuart Jon Spechler, Rhonda F Souza
Journal: Gut (2012)

<h3>Objective</h3> Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GORD) can have similar clinical and histological features. Proton pump inhibitors (PPIs) are used to distinguish the disorders, with the assumption that only GORD can respond to PPIs. Oesophageal expression of eotaxin-3 stimulated by Th2 cytokines might contribute to oesophageal eosinophilia in EoE. Th2 cytokine effects on the oesophagus in GORD are not known. The objective of the authors was to explore the molecular mechanisms of Th2 cytokines on eotaxin-3 expression by oesophageal squamous cells from patients with GORD and EoE, and the effects of omeprazole on that eotaxin-3 expression. <h3>Design</h3> Using telomerase-immortalised and primary cultures of oesophageal squamous cells from GORD and EoE patients, the authors measured eotaxin-3 protein secretion stimulated by Th2 cytokines (interleukin (IL)-4 and IL-13). Eotaxin-3 promoter constructs were used to study transcriptional regulation. Cytokine-induced eotaxin-3 mRNA and protein expression were measured in the presence or absence of omeprazole. <h3>Results</h3> There were no significant differences between EoE and GORD primary cells in cytokine-stimulated eotaxin-3 protein secretion levels. In EoE and GORD cell lines, IL-4 and IL-13 activated the eotaxin-3 promoter, and significantly increased eotaxin-3 mRNA and protein expression. Omeprazole blocked the cytokine-stimulated increase in eotaxin-3 mRNA and protein expression in EoE and GORD cell lines. <h3>Conclusion</h3> Oesophageal squamous cells from GORD and EoE patients express similar levels of eotaxin-3 when stimulated by Th2 cytokines, and omeprazole blocks that eotaxin-3 expression. These findings suggest that PPIs might have eosinophil-reducing effects independent of effects on acid reflux and that response to PPIs might not distinguish EoE from GORD.
DIET, NUTRITION, AND PROSTATE CANCER
Authors: Steven K. Clinton, Edward Giovannucci
Journal: Annual Review of Nutrition (1998)

▪ Abstract Cancer of the prostate gland is one of the most common malignancies in affluent nations, in part due to the application of new screening and diagnostic tools. The development of life-threatening prostate cancer is the culmination of a complex series of initiation and promotional events over a period of decades and under the influence of many interacting genetic and environmental factors. A rapidly accumulating scientific literature provides compelling evidence for the hypothesis that diet and nutrition are important factors modifying risk of prostate cancer. Additional resources devoted to interactive research efforts by laboratory scientists and epidemiologists will provide further enlightenment and continued refinement of our assessment of risks and benefits for specific nutrients and dietary patterns. These studies provide hope that evidence-based dietary interventions will significantly impact the risk of prostate cancer and enhance the efficacy of therapeutic interventions.