tbuckley/cabot-search huggingface dataset:
Effect of sodium bicarbonate ingestion upon repeated sprints.
Authors: G Lavender, S R Bird
Journal: British Journal of Sports Medicine (1989)

The purpose of the study was to assess the effect of sodium bicarbonate ingestion upon repeated bouts of intensive short duration exercise. Twenty-three subjects participated in the investigation (8 females and 15 males, age 21.4 +/- 2.3, mean +/- sd). Subjects completed six trials; three following the ingestion of sodium bicarbonate (300 mg/kg body weight) and three following the ingestion of a placebo (8 g sodium chloride). Each trial consisted of ten ten-second sprints on a cycle ergometer with 50 seconds recovery between each sprint. 'Peak power' and 'average power output' during each ten second sprint was measured from the flywheel of the ergometer using a light-sensitive monitor (Cranlea) linked to a BBC microcomputer. The power outputs recorded during each ten-second sprint of the bicarbonate trials were then compared with those recorded during the corresponding sprint of the placebo trials. The bicarbonate trials produced higher mean 'average power' outputs in all ten of the ten-second sprints, with the difference in 'average power' output being statistically significant in eight of these (p less than 0.05). The results also revealed that the difference in the 'average power' outputs attained during the bicarbonate and placebo trials increased as the number of sprint repetitions increased (p less than 0.01). 'Peak power' output was also greater in the bicarbonate trials with it being significantly higher (p less than 0.001) during the final ten-second sprint. It was concluded that during exercise consisting of repeated, short-duration sprints, power output was enhanced following the ingestion of sodium bicarbonate, (300 mg/kg body weight).
A Highly Specific Probe for Sensing Hydrogen Sulfide in Live Cells Based on Copper-Initiated Fluorogen with Aggregation-Induced Emission Characteristics
Authors: Xin Li, Chengyu Yang, Kai Wu, Yongzhou Hu, Yifeng Han, Steven H. Liang
Journal: Theranostics (2014)

Here we reported the first fluorescent probe with aggregation-induced emission characteristics, namely AIE-S, for the detection of hydrogen sulfide (H 2 S) in live cells.The detection system is selective for complicated biological application and the response is fast enough to complete within seconds.Moreover, the probe exhibits the unique advantage of being immune to aggregation-caused quenching which is a detrimental phenomenon limiting the application of most current available H 2 S fluorescent probes.The detection mechanism was investigated and postulated to be S 2-initiated de-coordination and thereafter aggregation of the AIE-S complex.
Clinical Significance of CD33 Nonsynonymous Single-Nucleotide Polymorphisms in Pediatric Patients with Acute Myeloid Leukemia Treated with Gemtuzumab-Ozogamicin–Containing Chemotherapy
Authors: Leslie Mortland, Todd A. Alonzo, Roland B. Walter, Robert B. Gerbing, Amit K. Mitra, Jessica A. Pollard, Michael R. Loken, Betsy Hirsch, Susana Raimondi, Janet Franklin, Stanley Pounds, Xueyuan Cao, Jeffrey E. Rubnitz, Raul C. Ribeiro, Alan Gamis, Soheil Meshinchi, Jatinder K. Lamba
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The purpose of this study was to evaluate clinical implications of CD33 single-nucleotide polymorphisms (SNP) in pediatric patients with acute myeloid leukemia (AML) treated with gemtuzumab-ozogamicin (GO)–based therapy. Experimental Design: We genotyped four CD33 SNPs: rs35112940 (G&amp;gt;A; Arg304Gly), rs12459419 (C&amp;gt;T; Ala14Val), rs2455069 (A&amp;gt;G; Arg69Gly), and rs1803254 (G&amp;gt;C; 3′UTR) in pediatric patients undergoing induction chemotherapy containing GO (COG-AAML03P1 trial; n = 242) or not containing GO (St. Jude AML02 trial; n = 172). Results: CD33 SNPs were correlated significantly with clinical characteristics and treatment outcome. The coding SNPs, rs35112940 and rs12459419, were significantly associated with clinical endpoints in COG-AAML03P1 but not in the St. Jude AML02 trial. Specifically, among white patients in COG-AAML03P1, the 3-year overall survival (OS) rate from remission was 84% ± 8% for those homozygous (GG) for rs35112940 versus 68% ± 15% for the other genotypes (P = 0.018); these patients also had a lower relapse risk and superior disease-free survival. Likewise, patients homozygous for variant allele (TT) for rs12459419 were more likely to have favorable risk disease than CC and CT genotypes (52% vs. 31%, P = 0.034) and significantly lower diagnostic blast CD33 expression than other genotypes (P &amp;lt; 0.001). Conclusion: Our data suggest that genetic variations in CD33 could impact clinical outcome of GO-based therapy in pediatric AMLs. Clin Cancer Res; 19(6); 1620–7. ©2013 AACR.
Prevalence of Adenomas and Hyperplastic Polyps in Mismatch Repair Mutation Carriers Among CAPP2 Participants: Report by the Colorectal Adenoma/Carcinoma Prevention Programme 2
Authors: Annelie Liljegren, Gail Barker, Faye Elliott, Lucio Bertario, Marie Luise Bisgaard, Diana Eccles, Gareth Evans, Finlay Macrae, Eamonn Maher, Annika Lindblom, Samuel Rotstein, Bo Nilsson, Jukka-Pekka Mecklin, Gabriela Möslein, Jeremy Jass, Riccardo Fodde, John Mathers, John Burn, D. Timothy Bishop
Journal: Journal of Clinical Oncology (2008)

To determine the prevalence of adenomatous and hyperplastic polyps in a large cohort of individuals with a germline mutation in a mismatch repair (MMR) gene, the major genetic determinant of hereditary nonpolyposis colorectal cancer (HNPCC). These prevalences have been estimated previously in smaller studies, and the results have been found to be variable.Colorectal Adenoma/Carcinoma Prevention Programme 2 trial is a chemoprevention trial in people classified as having HNPCC. The 695 patients with a proven germline MMR mutation and documented screening history before the chemoprevention study were the focus of this study. The number, histology, size, and location of polyps found at the participants' first ever colonoscopy were analyzed in a cross-sectional study.Seventy-four patients (10.6%) were found to have at least one adenoma at first colonoscopy, whereas 37 (5.3%) had at least one hyperplastic polyp. The frequency of an adenoma at first colonoscopy increased from 5.0% (95% CI, 2.8% to 8.3%) in patients younger than 35 years old to 18.9% (95% CI, 9.4% to 32.0%) in patients age at least 55 years (P = .0001 for trend). No such trend was observed for hyperplastic polyps. No sex differences were found for either type of polyp. A marginal association was found between the co-occurrence of adenomas and hyperplastic polyps. Adenomas tended to be more proximally distributed through the colon, whereas hyperplastic polyps tended to be located in the distal colon.Adenoma prevalence increases with age among MMR mutation carriers, whereas hyperplastic polyp prevalence is consistent. No sex differences were observed for either type of lesion.
Metabolic remodelling of the failing heart: beneficial or detrimental?
Authors: M. van Bilsen, F. A. van Nieuwenhoven, G. J. van der Vusse
Journal: Cardiovascular Research (2008)

The failing heart is characterized by alterations in energy metabolism, including mitochondrial dysfunction and a reduction in fatty acid (FA) oxidation rate, which is partially compensated by an increase in glucose utilization. Together, these changes lead to an impaired capacity to convert chemical energy into mechanical work. This has led to the concept that supporting cardiac energy conversion through metabolic interventions provides an important adjuvant therapy for heart failure. The potential success of such a therapy depends on whether the shift from FA towards glucose utilization should be considered beneficial or detrimental, a question still incompletely resolved. In this review, the current status of the literature is evaluated and possible causes of observed discrepancies are discussed. It is cautiously concluded that for the failing heart, from a therapeutic point of view, it is preferable to further stimulate glucose oxidation rather than to normalize substrate metabolism by stimulating FA utilization. Whether this also applies to the pre-stages of cardiac failure remains to be established.
MinK-Related Peptide 1
Authors: H. Yu, J. Wu, I. Potapova, R. T. Wymore, B. Holmes, J. Zuckerman, Z. Pan, H. Wang, W. Shi, R. B. Robinson, M. R. El-Maghrabi, W. Benjamin, J. Dixon, D. McKinnon, I. S. Cohen, R. Wymore
Journal: Circulation Research (2001)

Abstract —The HCN family of ion channel subunits underlies the currents I f in heart and I h and I q in the nervous system. In the present study, we demonstrate that minK-related peptide 1 (MiRP1) is a β subunit for the HCN family. As such, it enhances protein and current expression as well as accelerating the kinetics of activation. Because MiRP1 also functions as a β subunit for the cardiac delayed rectifier I Kr , these results suggest that this peptide may have the unique role of regulating both the inward and outward channels that underlie cardiac pacemaker activity. The full text of this article is available at http://www.circresaha.org.
Histone Deacetylase Inhibitors in Cancer Therapy
Authors: Andrew A. Lane, Bruce A. Chabner
Journal: Journal of Clinical Oncology (2009)

Purpose Epigenetic processes are implicated in cancer causation and progression. The acetylation status of histones regulates access of transcription factors to DNA and influences levels of gene expression. Histone deacetylase (HDAC) activity diminishes acetylation of histones, causing compaction of the DNA/histone complex. This compaction blocks gene transcription and inhibits differentiation, providing a rationale for developing HDAC inhibitors. Methods In this review, we explore the biology of the HDAC enzymes, summarize the pharmacologic properties of HDAC inhibitors, and examine results of selected clinical trials. We consider the potential of these inhibitors in combination therapy with targeted drugs and with cytotoxic chemotherapy. Results HDAC inhibitors promote growth arrest, differentiation, and apoptosis of tumor cells, with minimal effects on normal tissue. In addition to decompaction of the histone/DNA complex, HDAC inhibition also affects acetylation status and function of nonhistone proteins. HDAC inhibitors have demonstrated antitumor activity in clinical trials, and one drug of this class, vorinostat, is US Food and Drug Administration approved for the treatment of cutaneous T-cell lymphoma. Other inhibitors in advanced stages of clinical development, including depsipeptide and MGCD0103, differ from vorinostat in structure and isoenzyme specificity, and have shown activity against lymphoma, leukemia, and solid tumors. Promising preclinical activity in combination with cytotoxics, inhibitors of heat shock protein 90, and inhibitors of proteasome function have led to combination therapy trials. Conclusion HDAC inhibitors are an important emerging therapy with single-agent activity against multiple cancers, and have significant potential in combination use.
International Union of Pharmacology. XIX. The IUPHAR Receptor Code: A Proposal for an Alphanumeric Classification System
Authors: P.P.A. Humphrey, E.A. Barnard
Journal: Pharmacological Reviews (1998)

A generally accepted system for defining, characterizing, and classifying transmitter/hormone receptors is desirable for several reasons. First, pharmacologists need a common language so that ambiguity is not created by varied and inconsistent terminologies. It is estimated that a significant
Unexpected findings of variability in microRNAs suggest roles in human genetics
Authors: Stefano Volinia
Journal: Genome Medicine (2012)

Short RNA molecules were considered to be junk for decades, but in recent years they have been shown to have important functional roles. MicroRNAs (miRNAs) in particular have attracted much attention. They have been assumed to be highly conserved in humans and other species; however, a recent study published in Genome Medicine reveals an unexpected level of variability in human miRNAs, including variations within the seed region. This challenges the current view of miRNAs, and may explain previous reports of pathogenic mutations in miRNAs. See research article http://genomemedicine.com/content/4/8/62/abstract.
Phase II Trial of Temozolomide Plus the Matrix Metalloproteinase Inhibitor, Marimastat, in Recurrent and Progressive Glioblastoma Multiforme
Authors: M. D. Groves
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Novel therapies are needed for patients with recurrent glioblastoma multiforme (GBM). Because there is evidence that temozolomide (TMZ) has some activity in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are important in glioma cell invasion, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat (MRM) in patients with recurrent GBM was studied. PATIENTS AND METHODS: Forty-four patients with recurrent GBM after standard radiotherapy were enrolled. For 19 patients, this therapy was their first chemotherapy after tumor progression after irradiation; 25 others had received chemotherapy previously. TMZ 150 to 200 mg/m2 days 1 to 5 and MRM 50 mg days 8 to 28 was administered at 28-day intervals for two cycles; then patients were reevaluated. Treatment continued until progression of tumor or toxicity developed. RESULTS: Joint and tendon pain was the major therapy-related toxicity and was reported in 47% of patients. Five patients (11%) were removed from the study because of intolerable joint pain. For all patients, the progression-free survival (PFS) at 6 months was 39%. Median PFS was 17 weeks, median overall survival was 45 weeks, and 12-month PFS was 16%. CONCLUSION: The combination of TMZ and MRM resulted in a PFS at 6 months that exceeded the literature target by 29%. This drug combination met phase II study criteria; further study in recurrent patients with GBM might be warranted. Further study of therapy-induced joint pain is necessary.
Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes
Authors: Teresa WM Fan, Magda Kucia, Kacper Jankowski, Richard M Higashi, Janina Ratajczak, Marius Z Ratajczak, Andrew N Lane
Journal: Molecular Cancer (2008)

The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30) and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis.The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells.The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells. The data further show that the mitochondria remain functional in Krebs' cycle activity and respiratory electron transfer that enables continued accelerated glycolysis. This may be a common adaptive strategy in cancer cells.
Bortezomib Sensitizes Non–Hodgkin's Lymphoma Cells to Apoptosis Induced by Antibodies to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) Receptors TRAIL-R1 and TRAIL-R2
Authors: Mitchell R. Smith, Fang Jin, Indira Joshi
Journal: Clinical Cancer Research (2007)

Abstract Non–Hodgkin's lymphoma (NHL) is an increasingly common disease that, despite advances in antibody-targeted therapy, still requires novel therapeutic approaches. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) activates a major nonmitochondrial pathway for tumor cell killing through binding to a receptor family, some activating and some decoy. Agonistic antibodies to the receptors TRAIL-R1 and TRAIL-R2 can mimic many of the effects of TRAIL. We are investigating the effects of such agonistic antibodies, mapatumumab directed at TRAIL-R1 and lexatumumab directed at TRAIL-R2, on NHL cell lines. These antibodies induce apoptosis through caspase-8 but also activate BID to involve the mitochondrial pathway and activate caspase-9. In addition, we find signaling through both the nuclear factor-κB and c-Jun NH2-terminal kinase pathways. Because the proteasome inhibitor bortezomib also affects these pathways, we have investigated the combination of TRAIL-R antibodies and bortezomib and show enhanced apoptosis and signaling as well as enhanced killing of NHL cells in a severe combined immunodeficient mouse/human NHL cell line xenograft system. The combination of bortezomib and TRAIL signaling warrants further investigation as a therapeutic regimen. Understanding the multiple intracellular pathways of TRAIL activation may lead to rationally designed therapeutic trials.
Dynamic Repositioning of CD4 and CD8 Genes during T Cell Development
Authors: Stephanie Delaire, Yina Hsing Huang, Shaio Wei Chan, Ellen A. Robey
Journal: The Journal of Experimental Medicine (2004)

Although stable repression of CD4 and CD8 genes is a central feature of T cell lineage commitment, we lack detailed information about the timing and mechanism of this repression. Stable gene repression has been linked to the position of genes within the nucleus. Therefore, information about the nuclear position of CD4 and CD8 genes during T cell development could provide insights into both the mechanism of regulation of CD4 and CD8 genes, and the process of lineage commitment. Here, we report that lineage-specific repression of CD4 and CD8 genes is associated with the repositioning of alleles close to heterochromatin. We also provide evidence that the relocalization of CD4 and CD8 genes to heterochromatin can occur as an early response to positive selection signals. We discuss our results in terms of our current knowledge of CD4 and CD8 gene regulation and CD4 versus CD8 lineage commitment.
Prevention of age related macular degeneration
Authors: N. F Hall
Journal: BMJ (2002)

Papers p 11

Age related macular degeneration may be recognised in its early stages by the appearance of drusen and pigment change within the retina, but it produces few symptoms. Progression of age related macular degeneration can result in irreversible visual loss and is the commonest cause of blindness in the Western world. New treatments such as photodynamic therapy and macular surgery may limit the extent of visual loss and in a few cases even restore sight.1 But in contrast with cataract surgery, outcomes are unpredictable and the treatment is burdensome for patients and carries massive resource implications for healthcare providers. The prospect of prevention is thus very appealing from the public health perspective, not to mention that of the patient who may be at risk of losing the ability to recognise faces, read a newspaper, or to live independently. Increasing evidence suggests that cumulative oxidative damage increases risk of age related macular degeneration.2 But evidence from trials and reviews suggests that the antioxidant vitamin E, used alone, does not seem to have a protective effect against age related macular degeneration. …
Effects of Pyridoxine on Serum Protein Expression in Hepatoma-Bearing Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: G P Tryfiates
Journal: JNCI Journal of the National Cancer Institute (1981)

The effect of pyridoxine depletion on the expression of serum protein species in control and Morris hepatoma No. 7777-bearing rats was studied with polyacrylamide gel electrophoresis (PAGE). A group of 20 Buffalo female rats was fed ad libitum a complete diet lacking pyridoxine, whereas a similar group was fed the same diet with pyridoxine. After a 22-day feeding period, 12 animals from each group were inoculated with hepatoma No. 7777 cells in the thigh muscles of both hind legs and allowed to grow for 25 days. Sera were obtained from all animals by heart puncture under light ether anesthesia, and protein species were resolved by PAGE. Eight and four protein bands in the haptoglobin and postalbumin regions, respectively, were resolved from control rat serum, whereas sera from depleted animals had eight and three bands, respectively. Protein expression was facilitated by the presence of hepatomas. Ten and six protein bands were seen in the haptoglobin and postalbumin regions, respectively, upon PAGE of sera from control tumor-bearing rats. A positive synergistic effect between pyridoxine lack and tumor presence was also found. Twelve and five bands were resolved in the haptoglobin and postalbumin regions, respectively, when sera from pyridoxine-depleted tumor-bearing rats were electrophoresed. These results showed that vitamin B6, in addition to its well-known coenzymatic function, exercised a type of control over protein expression, which may be positive or negative depending on the nutritional and health status of the animal.