tbuckley/cabot-search huggingface dataset:
Effects of chronic growth hormone hypersecretion on intrinsic contractility, energetics, isomyosin pattern, and myosin adenosine triphosphatase activity of rat left ventricle.
Authors: J Timsit, B Riou, J Bertherat, C Wisnewsky, N S Kato, A S Weisberg, J Lubetzki, Y Lecarpentier, S Winegrad, J J Mercadier
Journal: Journal of Clinical Investigation (1990)

We studied papillary muscle mechanics and energetics, myosin phenotype, and ATPase activities in left ventricles from rats bearing a growth hormone (GH)--secreting tumor. 18 wk after tumor induction, animals exhibited a dramatic increase in body weight (+101% vs. controls) but no change in the ventricular weight/body weight ratio. The maximum isometric force of papillary muscles normalized per cross-sectional area rose markedly (+42%, P less than 0.05 vs. controls), whereas the maximum unloaded shortening velocity did not change. This was observed despite a marked isomyosin shift towards V3 (32 +/- 5% vs. 8 +/- 2% in controls, P less than 0.001). Increased curvature of the force-velocity relationship (+64%, P less than 0.05 vs. controls) indicated that the muscles contracted more economically, suggesting the involvement of V3 myosin. Total calcium- and actin-activated myosin ATPase activities assayed on quickly frozen left ventricular sections were similar in tumor-bearing rats and in controls. After alkaline preincubation, these activities only decreased in tumor-bearing rats, demonstrating that V3 enzymatic sites were involved in total ATPase activity. These data demonstrate that chronic GH hypersecretion in the rat leads to a unique pattern of myocardial adaptation which allows the muscle to improve its contractile performance and economy simultaneously, thanks to myosin phenoconversion and an increase in the number of active enzymatic sites.
Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk
Authors: C. Lestuzzi, E. Vaccher, R. Talamini, A. Lleshi, N. Meneguzzo, E. Viel, S. Scalone, L. Tartuferi, A. Buonadonna, L. Ejiofor, H.-J. Schmoll
Journal: Annals of Oncology (2014)

Effort-induced myocardial ischemia (EMI) has been seldom described. Aims of our study were (A) to evaluate the prevalence of EMI during long-lasting 5-FU infusion; (B) to identify possible risk factors of EMI during 5-FU infusion.For the purpose (A), we prospectively evaluated a group of patients undergoing in-hospital continuous infusion (c.i.) of 5-FU. Patients with rest ischemia were excluded. Among 358 consecutive patients, 21 (5.9%) had rest ischemia; 109 could not perform a stress test. The remaining 228 patients underwent a treadmill stress test (TST) after >46 h of 5-FU infusion. For the purpose (B), we compared the characteristics of patients with EMI (including 3 previously described in a 2001 paper) with those without EMI.Among 228 patients, 16 (6.9%) had EMI. These 16 had a second TST after stopping 5-FU: in 14, it was negative, 2 patients with coronary artery disease had milder ischemia. The whole group of 231 (including 3 described in a previous paper) patients undergoing TST included 148 males and 83 females, with mean age of 57.5. Cardiovascular risk factors were present in 178 of them. Eight patients had ischemic heart disease. Among 19 patients with EMI, 7 had angina, 12 silent ischemia. ST segment at ECG was elevated in 10 patients, depressed in 9. Comparing the group with toxicity and the one without, the only significant difference was the complaint of atypical symptoms at rest before the TST. No difference was observed as regards: chemotherapy schedule (chronic c.i. in 49, 5 days in 178, FOLFOX type in 12), coronary risk factors or heart disease.EMI is as frequent as rest ischemia during 5-FU infusion. Patients undergoing 5-FU continuous infusions should be adviced to avoid unusual efforts, to refer any cardiac symptom, and should be investigated for EMI.
FLG (filaggrin) null mutations and sunlight exposure: Evidence of a correlation
Authors: Raffaella Cascella, Claudia Strafella, Chiara Germani, Laura Manzo, Luigi Tonino Marsella, Paola Borgiani, Nagat Sobhy, Rania Abdelmaksood, Spyros Gerou, Demetrios Ioannides, Federica Sangiuolo, Giuseppe Novelli, Doaa Hashad, Efstratios Vakirlis, Emiliano Giardina
Journal: Journal of the American Academy of Dermatology (2015)
Osteoprotegerin: A Novel Independent Marker for Silent Myocardial Ischemia in Asymptomatic Diabetic Patients
Authors: Antoine Avignon, Ariane Sultan, Christophe Piot, Denis Mariano-Goulart, Jean-François Thuan dit Dieudonné, Jean Paul Cristol, Anne Marie Dupuy
Journal: Diabetes Care (2007)

We sought to evaluate osteoprotegerin, an inhibitor of osteoclastogenesis involved in atherosclerosis, and other novel risk factors as predictive markers of silent myocardial ischemia (SMI).A total of 465 consecutive diabetic patients with more than one additional risk factor were evaluated for SMI using stress myocardial perfusion imaging (MPI). We studied the association of SMI (positive stress electrocardiogram and/or abnormal MPI) with osteoprotegerin, other novel risk factors (lipoprotein[a], homocysteine, adiponectin, C-reactive protein, and fibrinogen), and conventional risk factors (total, LDL, and HDL cholesterol and triglycerides).A total of 92 patients were diagnosed with SMI. Of the six novel markers, osteoprotegerin was the only one associated with SMI; the relative risk (RR) of SMI in patients with osteoprotegerin values above the 75th percentile was 3.19 (95% CI 1.99-5.18; P < 0.001) in comparison with those with osteoprotegerin below the 75th percentile. In univariate analyses, the other plasma markers significantly associated with SMI were higher triglycerides (P = 0.04) and lower HDL cholesterol (P = 0.02). The association of osteoprotegerin with SMI remained significant after correcting for other variables associated with SMI at P < 0.15 in univariate analysis (RR 3.95 [95% CI 2.21-7.06]; P < 0.0001). The association of osteoprotegerin with SMI was observed in male (P < 0.0001) and female (P = 0.03) patients, in type 1 (P = 0.002) and type 2 (P = 0.0004) diabetic patients, in patients with (P = 0.0004) or without (P = 0.03) nephropathy, and in patients without (P < 0.0001) but not with (P = 0.2) peripheral arterial disease.Osteoprotegerin measurement, together with other conventional factors, can help to better define the diabetic population with an increased likelihood for SMI.
Platyzoan Paraphyly Based on Phylogenomic Data Supports a Noncoelomate Ancestry of Spiralia
Authors: Torsten H. Struck, Alexandra R. Wey-Fabrizius, Anja Golombek, Lars Hering, Anne Weigert, Christoph Bleidorn, Sabrina Klebow, Nataliia Iakovenko, Bernhard Hausdorf, Malte Petersen, Patrick Kück, Holger Herlyn, Thomas Hankeln
Journal: Molecular Biology and Evolution (2014)

Based on molecular data three major clades have been recognized within Bilateria: Deuterostomia, Ecdysozoa, and Spiralia. Within Spiralia, small-sized and simply organized animals such as flatworms, gastrotrichs, and gnathostomulids have recently been grouped together as Platyzoa. However, the representation of putative platyzoans was low in the respective molecular phylogenetic studies, in terms of both, taxon number and sequence data. Furthermore, increased substitution rates in platyzoan taxa raised the possibility that monophyletic Platyzoa represents an artifact due to long-branch attraction. In order to overcome such problems, we employed a phylogenomic approach, thereby substantially increasing 1) the number of sampled species within Platyzoa and 2) species-specific sequence coverage in data sets of up to 82,162 amino acid positions. Using established and new measures (long-branch score), we disentangled phylogenetic signal from misleading effects such as long-branch attraction. In doing so, our phylogenomic analyses did not recover a monophyletic origin of platyzoan taxa that, instead, appeared paraphyletic with respect to the other spiralians. Platyhelminthes and Gastrotricha formed a monophylum, which we name Rouphozoa. To the exclusion of Gnathifera, Rouphozoa and all other spiralians represent a monophyletic group, which we name Platytrochozoa. Platyzoan paraphyly suggests that the last common ancestor of Spiralia was a simple-bodied organism lacking coelomic cavities, segmentation, and complex brain structures, and that more complex animals such as annelids evolved from such a simply organized ancestor. This conclusion contradicts alternative evolutionary scenarios proposing an annelid-like ancestor of Bilateria and Spiralia and several independent events of secondary reduction.
Redundancy: A Critical Obstacle to Improving Cancer Therapy
Authors: Orit Lavi
Journal: Cancer Research (2015)

A system characterized by redundancy has various elements that are able to act in the same biologic or dynamic manner, where the inhibition of one of those elements has no significant effect on the global biologic outcome or on the system's dynamic behavior. Methods that aim to predict the effectiveness of cancer therapies must include evolutionary and dynamic features that would change the static view that is widely accepted. Here, we explore several important issues about mechanisms of redundancy, heterogeneity, biologic importance, and drug resistance and describe methodologic challenges that, if overcome, would significantly contribute to cancer research.
Ingenuity Network-Assisted Transcription Profiling: Identification of a New Pharmacologic Mechanism for MK886
Authors: Anatoly L. Mayburd, Alfredo Martlínez, Daniel Sackett, Huaitian Liu, Joanna Shih, Jordy Tauler, Ingalill Avis, James L. Mulshine
Journal: Clinical Cancer Research (2006)

Abstract The small molecular inhibitor MK886 is known to block 5-lipoxygenase-activating protein ALOX5AP and shows antitumor activity in multiple human cell lines. The broad antitumor therapeutic window reported in vivo for MK886 in rodents supports further consideration of this structural class. Better understanding of the mode of action of the drug is important for application in humans to take place. Affymetrix microarray study was conducted to explore MK886 pharmacologic mechanism. Ingenuity Pathway Analysis software was applied to validate the results at the transcriptional level by putting them in the context of an experimental proteomic network. Genes most affected by MK886 included actin B and focal adhesion components. A subsequent National Cancer Institute-60 panel study, RT-PCR validation followed by confocal microscopy, and Western blotting also pointed to actin B down-regulation, filamentous actin loss, and disorganization of the transcription machinery. In agreement with these observations, MK886 was found to enhance the effect of UV radiation in H720 lung cancer cell line. In light of the modification of cytoskeleton and cell motility by lipid phosphoinositide 3-kinase products, MK886 interaction with actin B might be biologically important. The low toxicity of MK886 in vivo was modeled and explained by binding and transport by dietary lipids. The rate of lipid absorbance is generally higher for tumors, suggesting a promise of a targeted liposome-based delivery system for this drug. These results suggest a novel antitumor pharmacologic mechanism.
Wound prophylaxis in thoracic surgery: a new approach.
Authors: W S Walker, A Faichney, T Raychaudhury, R J Prescott, M A Calder, C T Sang, E W Cameron, P R Walbaum
Journal: Thorax (1984)

A prospective double blind, randomised study was performed in 100 patients undergoing major elective thoracic surgery to assess a new method of prophylaxis of wound infection using one preincisional intraparietal infiltration of cefuroxime sodium along the line of proposed incision as the sole protection against wound infection. A significant (p less than 0.01) reduction in the incidence of wound infection occurred in the antibiotic treated group (2%) compared with the control group (20%), who received by the same route the same volume of saline only. The groups were comparable with respect to age, sex, pathological condition, and operative variables. The use of additional antibiotics was significantly greater in the control group (p less than 0.01), largely owing to a much greater incidence of postoperative pulmonary infection in the control group (60%) than in the antibiotic treated group (40%). No morbidity was associated with this technique. The organisms found in oesophageal and bronchial operative luminal specimens did not correlate with postoperative wound or pulmonary infection or with organisms causing these infections. Reductions in wound and pulmonary infection rates equivalent to those produced by conventional multiple dose parenteral regimens were achieved by this technique.
Effect of heparin anticoagulation on neutrophil adhesion molecules and release of IL8: C3 is not essential
Authors: M. H. El Habbal, L. Smith, M. J. Elliott, S. Strobel
Journal: Cardiovascular Research (1995)

Journal Article Effect of heparin anticoagulation on neutrophil adhesion molecules and release of IL8: C3 is not essential Get access Magdi H. El Habbal, Magdi H. El Habbal * Cardiothoracic Unit and Host Defence Unit, The Institute of Child Health and The Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK *Corresponding author. Tel. 071-405 9200; Fax 071-813 8291. Search for other works by this author on: Oxford Academic PubMed Google Scholar Linda Smith, Linda Smith Cardiothoracic Unit and Host Defence Unit, The Institute of Child Health and The Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin J. Elliott, Martin J. Elliott Cardiothoracic Unit and Host Defence Unit, The Institute of Child Health and The Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephan Strobel Stephan Strobel Cardiothoracic Unit and Host Defence Unit, The Institute of Child Health and The Great Ormond Street Hospital for Children NHS Trust, London WC1N 3JH, UK Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 30, Issue 5, November 1995, Pages 676–681, https://doi.org/10.1016/S0008-6363(95)00069-0 Published: 01 November 1995 Article history Received: 06 February 1995 Accepted: 24 May 1995 Published: 01 November 1995
Risk of Breast Cancer in Relation to Lifetime Alcohol Consumption
Authors: M. P. Longnecker, P. A. Newcomb, R. Mittendorf, E. R. Greenberg, R. W. Clapp, G. F. Bogdan, J. Baron, B. MacMahon, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1995)

Although an association between alcohol consumption and risk of breast cancer has been observed in many studies, questions of major importance remain, including the nature of the dose-response relationship and the effects of drinking at various periods in life.Our goal was to address the issues listed above with a large case-control study.We conducted a population-based case-control study in Maine, Massachusetts (excluding the four counties that include metropolitan Boston), New Hampshire, and Wisconsin. Case patients were eligible if their diagnosis of invasive breast cancer was first reported to one of the four statewide cancer registries during the period of 1988 through 1991. During the accrual period, 11,879 potentially eligible case patients and 16,217 control subjects were identified. After excluding ineligible women from the study, telephone interviews were obtained from 6888 case patients and 9424 control subjects. Complete data for recent alcohol consumption, and thus final eligibility for study participation, were determined for 6662 case patients and 9163 control subjects. The average age at time of interview was 58.7 years. The questions on alcohol use addressed average consumption during five periods of the subjects' lives: ages 16-19, 20-29, 30-39, 40-59, and 60-74 years. Similar responses from 211 control subjects upon reinterview 6-12 months later were taken to be indicative of the reliability of the questionnaire used in this study.Lifetime average alcohol consumption (measured as the average grams per day consumed from age 16 to the recent past) and recent alcohol consumption (average grams per day consumed in the previous age interval) were associated with risk of developing breast cancer. The multivariate relative risk of breast cancer, in those who drink compared with abstainers, associated with average lifetime consumption of 12-18 g/day of alcohol (about one drink) was 1.39 (95% confidence interval [CI] = 1.16-1.67), of 19-32 g/day (about two drinks) was 1.69 (95% CI = 1.36-2.10), of 33-45 g/day (about three drinks) was 2.30 (95% CI = 1.51-3.51), and of greater than or equal to 46 g/day (four or more drinks) was 1.75 (95% CI = 1.16-2.64) (P for trend < .0001). The multivariate relative risk per 13 g/day (about one drink) of alcohol consumed before 30 years of age was 1.09 (95% CI = 0.95-1.24), whereas the relative risk associated with recent consumption of 13 g/day was 1.21 (95% CI = 1.09-1.34).In these data, alcohol consumption was clearly related to breast cancer risk. Risk appeared to increase even at moderate levels of consumption. For women of all ages combined, consumption before 30 years of age was not an important determinant of risk.
Tumor cells transfected with a bacterial heat-shock gene lose tumorigenicity and induce protection against tumors.
Authors: K V Lukacs, D B Lowrie, R W Stokes, M J Colston
Journal: The Journal of Experimental Medicine (1993)

The gene encoding a highly immunogenic mycobacterial heat-shock protein (hsp65) was transfected into the murine macrophage tumor cell line J774. The resulting hsp65-expressing cells (J774-hsp65) were no longer able to produce tumors in syngeneic mice. This loss of tumorigenicity was not mediated through T cells since the transfected cells did not produce tumors in athymic mice. If mice are first immunized with the J774-hsp65 cells and then challenged with the parent J774 cells, the mice do not develop tumors, indicating that the presence of the mycobacterial hsp65 protein greatly enhances immunological recognition of unique structures expressed by the parent tumor cells. This is further confirmed by the demonstration in vitro of T cells derived from J774-hsp65-immunized mice that are cytotoxic for the parent J774 cells. The results provide the basis for a novel strategy for enhancing the immunological recognition and decreasing the tumorigenicity of transformed cells.
The Role of High-Dose Chemotherapy and Stem-Cell Transplantation in Patients with Multiple Myeloma: A Practice Guideline of the Cancer Care Ontario Practice Guidelines Initiative
Authors: Kevin Imrie, Rosmin Esmail, Ralph M. Meyer
Journal: Annals of Internal Medicine (2002)

The Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative has systematically reviewed the published literature and, through a consensus process, developed an evidence-based practice guideline assessing the role of stem-cell transplantation in patients with multiple myeloma. The conclusions were validated by solicited feedback from 221 practitioners across Ontario, Canada. The guideline comprises six recommendations: 1) Autologous transplantation is recommended for patients with stage II or III myeloma and good performance status. Evidence of benefit is strongest for patients who are younger than 55 years of age and have a serum creatinine level less than 150 µmol/L [<1.7 mg/dL]. Physicians must use clinical judgment in recommending transplantation to other patients. 2) Allogeneic transplantation is not recommended as routine therapy. 3) Patients potentially eligible for transplantation should be referred for assessment early after diagnosis and should not be extensively exposed to alkylating agents before collection of stem cells. 4) Autologous peripheral blood stem cells should be harvested early in the patient's treatment course. The best available data suggest that transplantation is most advantageous when performed as part of initial therapy. 5) The comparative data addressing the specifics of the transplantation process are insufficient to allow definitive recommendations. In the absence of such data, a single transplant with high-dose melphalan, with or without total-body irradiation, is suggested for patients undergoing transplantation outside a clinical trial. 6) At this time, no conclusions can be reached about the role of interferon therapy after transplantation. *For members of the Hematology Disease Site Group of the Cancer Care Ontario Practice Guidelines Initiative, see Appendix.
HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin–TCF interaction
Authors: Feng Ye, Ying Chen, ThaoNguyen Hoang, Rusty L Montgomery, Xian-hui Zhao, Hong Bu, Tom Hu, Makoto M Taketo, Johan H van Es, Hans Clevers, Jenny Hsieh, Rhonda Bassel-Duby, Eric N Olson, Q Richard Lu
Journal: Nature Neuroscience (2009)
Adaptive Evolution of Four Microcephaly Genes and the Evolution of Brain Size in Anthropoid Primates
Authors: S. H. Montgomery, I. Capellini, C. Venditti, R. A. Barton, N. I. Mundy
Journal: Molecular Biology and Evolution (2010)

The anatomical basis and adaptive function of the expansion in primate brain size have long been studied; however, we are only beginning to understand the genetic basis of these evolutionary changes. Genes linked to human primary microcephaly have received much attention as they have accelerated evolutionary rates along lineages leading to humans. However, these studies focus narrowly on apes, and the link between microcephaly gene evolution and brain evolution is disputed. We analyzed the molecular evolution of four genes associated with microcephaly (ASPM, CDK5RAP2, CENPJ, MCPH1) across 21 species representing all major clades of anthropoid primates. Contrary to prevailing assumptions, positive selection was not limited to or intensified along the lineage leading to humans. In fact we show that all four loci were subject to positive selection across the anthropoid primate phylogeny. We developed clearly defined hypotheses to explicitly test if selection on these loci was associated with the evolution of brain size. We found positive relationships between both CDK5RAP2 and ASPM and neonatal brain mass and somewhat weaker relationships between these genes and adult brain size. In contrast, there is no evidence linking CENPJ and MCPH1 to brain size evolution. The stronger association of ASPM and CDK5RAP2 evolution with neonatal brain size than with adult brain size is consistent with these loci having a direct effect on prenatal neuronal proliferation. These results suggest that primate brain size may have at least a partially conserved genetic basis. Our results contradict a previous study that linked adaptive evolution of ASPM to changes in relative cortex size; however, our analysis indicates that this conclusion is not robust. Our finding that the coding regions of two widely expressed loci has experienced pervasive positive selection in relation to a complex, quantitative developmental phenotype provides a notable counterexample to the commonly asserted hypothesis that cis-regulatory regions play a dominant role in phenotypic evolution.
Second-line chemotherapy with temozolomide in recurrent oligodendroglioma after PCV (procarbazine, lomustine and vincristine) chemotherapy: EORTC Brain Tumor Group phase II study 26972
Authors: M.J. van den Bent, O. Chinot, W. Boogerd, J. Bravo Marques, M.J.B. Taphoorn, J.M. Kros, C.C.D. van der Rijt, C.J. Vecht, N. De Beule, B. Baron
Journal: Annals of Oncology (2003)
Novel Technique to Prevent Left Phrenic Nerve Injury During Epicardial Catheter Ablation
Authors: Seiichiro Matsuo, Pierre Jaïs, Sebastien Knecht, Kang-Teng Lim, Mélèze Hocini, Nicolas Derval, Matthew Wright, Frederic Sacher, Michel Haïssaguerre
Journal: Circulation (2008)