tbuckley/cabot-search huggingface dataset:
Effects of Exemestane Administered for 2 Years Versus Placebo on Bone Mineral Density, Bone Biomarkers, and Plasma Lipids in Patients With Surgically Resected Early Breast Cancer
Authors: Per E. Lønning, Jürgen Geisler, Lars E. Krag, Bjørn Erikstein, Yngve Bremnes, Anne I. Hagen, Ellen Schlichting, Ernst A. Lien, Erik S. Øfjord, Jolanda Paolini, Anna Polli, Giorgio Massimini
Journal: Journal of Clinical Oncology (2005)

To evaluate potential detrimental effects of exemestane on bone and lipid metabolism.Postmenopausal women with early breast cancer were randomly assigned to exemestane 25 mg daily or placebo for 2 years in a double-blind setting. Primary objective was to evaluate the effect of exemestane on bone mineral density. Secondary objectives were effects on bone biomarkers, plasma lipids, coagulation factors, and homocysteine. Planned size was 128 patients.One hundred forty-seven patients were enrolled. All patients completed their 24-month visit except for those discontinuing treatment at an earlier stage. The mean annual rate of bone mineral density loss was 2.17% v 1.84% in the lumbar spine (P = .568) and 2.72% v 1.48% in the femoral neck (P = .024) in the exemestane and placebo arm, respectively. The mean change in T-score after 2 years was -0.21 for exemestane and -0.11 on placebo in the hip, and -0.30 and -0.21, respectively, in the lumbar spine. Exemestane significantly increased serum level and urinary excretion of bone resorption, but also bone formation markers. Except for a modest reduction in high-density lipoprotein cholesterol (P < .001) and apolipoprotein A1 (P = .004), exemestane had no major effect on lipid profile, homocysteine levels, or coagulation parameters.Exemestane modestly enhanced bone loss from the femoral neck without significant influence on lumbar bone loss. Except for a 6% to 9% drop in plasma high-density lipoprotein cholesterol, no major effects on serum lipids, coagulation factors, or homocysteine were recorded. Bone mineral density should be assessed according to the US Preventive Services Task Force guidelines.
Elevated serum human growth hormone and decreased serum insulin in prediabetic males after intravenous tolbutamide and glucose
Authors: G. Boden, J. S. Soeldner, R. E. Gleason, A. Marble
Journal: Journal of Clinical Investigation (1968)

Serum human growth hormone (HGH), serum immunoreactive insulin (IRI), plasma free fatty acids, and blood glucose were measured during intravenous glucose and intravenous tolbutamide tolerance tests in 13 normal and 13 prediabetic (offspring of two diabetic parents) males, closely matched for weight and age. Only prediabetics with normal glucose tolerance during oral, intravenous, and cortisone-primed glucose tolerance tests were evaluated. Mean serum HGH levels were significantly higher in prediabetics in response to intravenous tolbutamide and at the end of the 3-hr intravenous glucose tolerance tests (IVGTT). This is interpreted as a hyperresponsiveness of the growth hormone-releasing mechanisms in prediabetic subjects. The insulin response during the first 10 min of an IVGTT was significantly reduced in prediabetic males as compared to normal controls, whereas the insulin response to intravenous tolbutamide was not significantly different at the same time intervals in the same subjects.It appears, therefore, that measuring IRI during an IVGTT can be valuable in detecting the earliest signs of diabetes even before any disturbance of blood glucose homeostasis is seen. The possibility that growth hormone hypersecretion in prediabetics might play a role in the pathogenesis of human diabetes mellitus is discussed.
MicroRNA 217 Modulates Endothelial Cell Senescence via Silent Information Regulator 1
Authors: Rossella Menghini, Viviana Casagrande, Marina Cardellini, Eugenio Martelli, Alessandro Terrinoni, Francesca Amati, Mariuca Vasa-Nicotera, Arnaldo Ippoliti, Giuseppe Novelli, Gerry Melino, Renato Lauro, Massimo Federici
Journal: Circulation (2009)

Aging is a major risk factor for the development of atherosclerosis and coronary artery disease. Through a microarray approach, we have identified a microRNA (miR-217) that is progressively expressed in endothelial cells with aging. miR-217 regulates the expression of silent information regulator 1 (SirT1), a major regulator of longevity and metabolic disorders that is progressively reduced in multiple tissues during aging.miR-217 inhibits SirT1 expression through a miR-217-binding site within the 3'-UTR of SirT1. In young human umbilical vein endothelial cells, human aortic endothelial cells, and human coronary artery endothelial cells, miR-217 induces a premature senescence-like phenotype and leads to an impairment in angiogenesis via inhibition of SirT1 and modulation of FoxO1 (forkhead box O1) and endothelial nitric oxide synthase acetylation. Conversely, inhibition of miR-217 in old endothelial cells ultimately reduces senescence and increases angiogenic activity via an increase in SirT1. miR-217 is expressed in human atherosclerotic lesions and is negatively correlated with SirT1 expression and with FoxO1 acetylation status.Our data pinpoint miR-217 as an endogenous inhibitor of SirT1, which promotes endothelial senescence and is potentially amenable to therapeutic manipulation for prevention of endothelial dysfunction in metabolic disorders.
The Evolution of Chloroplast RNA Editing
Authors: Michael Tillich, Pascal Lehwark, Brian R Morton, Uwe G Maier
Journal: Molecular Biology and Evolution (2006)

RNA editing alters the nucleotide sequence of an RNA molecule so that it deviates from the sequence of its DNA template. Different RNA-editing systems are found in the major eukaryotic lineages, and these systems are thought to have evolved independently. In this study, we provide a detailed analysis of data on C-to-U editing sites in land plant chloroplasts and propose a model for the evolution of RNA editing in land plants. First, our data suggest that the limited RNA-editing system of seed plants and the much more extensive systems found in hornworts and ferns are of monophyletic origin. Further, although some eukaryotic editing systems appear to have evolved to regulate gene expression, or at least are now involved in gene regulation, there is no evidence that RNA editing plays a role in gene regulation in land plant chloroplasts. Instead, our results suggest that land plant chloroplast C-to-U RNA editing originated as a mechanism to generate variation at the RNA level, which could complement variation at the DNA level. Under this model, many of the original sites, particularly in seed plants, have been subsequently lost due to mutation at the DNA level, and the function of extant sites is merely to conserve certain codons. This is the first comprehensive model for the evolution of the chloroplast RNA-editing system of land plants and may also be applicable to the evolution of RNA editing in plant mitochondria.
Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study
Authors: Martin J Elliott, Paolo De Coppi, Simone Speggiorin, Derek Roebuck, Colin R Butler, Edward Samuel, Claire Crowley, Clare McLaren, Anja Fierens, David Vondrys, Lesley Cochrane, Christopher Jephson, Samuel Janes, Nicholas J Beaumont, Tristan Cogan, Augustinus Bader, Alexander M Seifalian, J Justin Hsuan, Mark W Lowdell, Martin A Birchall
Journal: The Lancet (2012)
Fruit and Vegetable Intake and Risk of Major Chronic Disease
Authors: H.-C. Hung, K. J. Joshipura, R. Jiang, F. B. Hu, D. Hunter, S. A. Smith-Warner, G. A. Colditz, B. Rosner, D. Spiegelman, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (2004)

Studies of fruit and vegetable consumption in relation to overall health are limited. We evaluated the relationship between fruit and vegetable intake and the incidence of cardiovascular disease and cancer and of deaths from other causes in two prospective cohorts.A total of 71 910 female participants in the Nurses' Health study and 37,725 male participants in the Health Professionals' Follow-up Study who were free of major chronic disease completed baseline semiquantitative food-frequency questionnaires in 1984 and 1986, respectively. Dietary information was updated in 1986, 1990, and 1994 for women and in 1990 and 1994 for men. Participants were followed up for incidence of cardiovascular disease, cancer, or death through May 1998 (women) and January 1998 (men). Multivariable-adjusted relative risks were calculated with Cox proportional hazards analysis.We ascertained 9329 events (1964 cardiovascular, 6584 cancer, and 781 other deaths) in women and 4957 events (1670 cardiovascular diseases, 2500 cancers, and 787 other deaths) in men during follow-up. For men and women combined, participants in the highest quintile of total fruit and vegetable intake had a relative risk for major chronic disease of 0.95 (95% confidence interval [CI] = 0.89 to 1.01) times that of those in the lowest. Total fruit and vegetable intake was inversely associated with risk of cardiovascular disease but not with overall cancer incidence, with relative risk for an increment of five servings daily of 0.88 (95% CI = 0.81 to 0.95) for cardiovascular disease and 1.00 (95% CI = 0.95 to 1.05) for cancer. Of the food groups analyzed, green leafy vegetable intake showed the strongest inverse association with major chronic disease and cardiovascular disease. For an increment of one serving per day of green leafy vegetables, relative risks were 0.95 (95% CI = 0.92 to 0.99) for major chronic disease and 0.89 (95% CI = 0.83 to 0.96) for cardiovascular disease.Increased fruit and vegetable consumption was associated with a modest although not statistically significant reduction in the development of major chronic disease. The benefits appeared to be primarily for cardiovascular disease and not for cancer.
Viral Dynamics of Acute HIV-1 Infection
Authors: Susan J. Little, Angela R. McLean, Celsa A. Spina, Douglas D. Richman, Diane V. Havlir
Journal: The Journal of Experimental Medicine (1999)

Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R0), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (α) was highly variable among individuals. The phase 1 viral decay rate (δI = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R0) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection.
Prognostic nomogram for patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization
Authors: Li Xu, Zhen-Wei Peng, Min-Shan Chen, Ming Shi, Yao-Jun Zhang, Rong-Ping Guo, Xiao-Jun Lin, Wan-Yee Lau
Journal: Journal of Hepatology (2015)
S <sup>2</sup> Connector Versus Suture
Authors: Willem J.L. Suyker, John P. Matonick, Paul T.W. Suyker, Aart Brutel de la Rivière, Marc P. Buijsrogge, Ricardo P.J. Budde, Cees W.J. Verlaan, Gerard Pasterkamp, Paul F. Gründeman, Cornelius Borst
Journal: Circulation (2006)

Background— Anastomotic connectors could be the key to less invasive bypass surgery, including endoscopic procedures, but equivalence to conventional suturing needs to be established. A novel distal coronary connector was tested pre-clinically for safety and efficacy in comparison to conventional suturing. Methods and Results— Left internal thoracic to left anterior descending coronary artery bypasses were constructed off-pump in 35 pigs (73±8 kg). An intraluminal metal connector (S 2 AS) was used in 21 and conventional suturing in 14 animals. S 2 AS anastomosis construction was easier achieved in one-fourth of the conventional construction time (3.7±0.7 versus 16.5±2.6 minutes; P &lt;0.001). Acute patency tended to be better ( P =0.15). All anastomoses were evaluated intraoperatively, and subgroups at 90 and at 180 days. Patency was 100%. An effective remodeling response was observed in all groups, resulting in unobstructed anastomoses with excellent hemodynamic performance (fractional flow reserve ≥0.93 at 180 days). At 6 months, the noncompliant connector was covered with stabilized neointima that was thinner than found on the suture line (0.10±0.04 versus 0.31±0.13 mm; P =0.01). The connector induced less lumen loss (−0.6±6.5 versus 21.6±19%; P =0.03). The initial side-to-side configuration had remodeled to an end-to-side shape as intended. Conclusions— In the porcine model, the connector rapidly and consistently produced high-quality anastomoses that fully met current standards on patency and function. Unconventional aspects like a noncompliant intraluminal ring and a side-to-side to end-to-side converted configuration did not interfere with favorable anastomosis remodeling. These findings shed a new light on the anatomical prerequisites for anastomosis patency.
Rates of Genome Evolution and Branching Order from Whole Genome Analysis
Authors: Gavin A. Huttley, Matthew J. Wakefield, Simon Easteal
Journal: Molecular Biology and Evolution (2007)

Accurate estimation of any phylogeny is important as a framework for evolutionary analysis of form and function at all levels of organization from sequence to whole organism. Using alignments of nonrepetitive components of opossum, human, mouse, rat, and dog genomes we evaluated two alternative tree topologies for eutherian evolution. We show with very high confidence that there is a basal split between rodents (as represented by the mouse and rat) and a branch joining primates (as represented by humans) and carnivores (as represented by dogs), consistent with some but not the most widely accepted mammalian phylogenies. The result was robust to substitution model choice with equivalent inference returned from a spectrum of models ranging from a general time reversible model, a model that treated nucleotides as either purines and pyrimidines, and variants of these that incorporated rate heterogeneity among sites. By determining this particular branching order we are able to show that the rate of molecular evolution is almost identical in rodent and carnivore lineages and that sequences evolve ∼11%–14% faster in these lineages than in the primate lineage. In addition by applying the chicken as outgroup the analyses suggested that the rate of evolution in all eutherian lineages is ∼30% slower than in the opossum lineage. This pattern of relative rates is inconsistent with the hypothesis that generation time is an important determinant of substitution rates and, by implication, mutation rates. Possible factors causing rate differences between the lineages include differences in DNA repair and replication enzymology, and shifts in nucleotide pools. Our analysis demonstrates the importance of using multiple sequences from across the genome to estimate phylogeny and relative evolutionary rate in order to reduce the influence of distorting local effects evident even in relatively long sequences.
Endothelial cell biology in relation to current concepts of vessel wall structure and function.
Authors: P A Marsden, M S Goligorsky, B M Brenner
Journal: Journal of the American Society of Nephrology (1991)

Vascular endothelium is now appreciated to modulate vessel wall structure and function in health and disease. Strategically located between the intravascular space and vessel wall proper, the endothelium has a broad capacity to modify the functional state of adjacent or trafficking cells. Furthermore, recent findings indicate that the endothelium is an interactive tissue capable of responding to numerous mechanical, chemical, and cellular stimuli. The focus of this review will be a discussion of endothelial cell biology in relation to vascular structure and function, with particular emphasis on endothelial modulation of vasomotor tone. It is evident that endothelial cells contribute to the local control of vascular tone by releasing potent vasodilatory mediators, such as endothelium-derived relaxing factor, and vasoconstrictor mediators such as endothelin-1. The endothelium also serves to modify blood-borne signals to which vascular tissues respond. The kidney shares, directly and indirectly, in these events, making this emerging new area a focus of major interest for nephrologists.
Consensus Recommendations to Accelerate Clinical Trials for Neurofibromatosis Type 2
Authors: D. Gareth Evans, Michel Kalamarides, Kim Hunter-Schaedle, Jaishri Blakeley, Jeffrey Allen, Dusica Babovic-Vuskanovic, Allan Belzberg, Gideon Bollag, Ruihong Chen, Emmanuelle DiTomaso, John Golfinos, Gordon Harris, Abraham Jacob, Ganjam Kalpana, Matthias Karajannis, Bruce Korf, Razelle Kurzrock, Meng Law, Andrea McClatchey, Roger Packer, Pamela Roehm, Allan Rubenstein, William Slattery, James H. Tonsgard, D. Bradley Welling, Brigitte Widemann, Kaleb Yohay, Marco Giovannini
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. Experimental Design: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. Results: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. Conclusions: Both phase 0 and phase II NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics. (Clin Cancer Res 2009;15(16):5032–9)
Abstract 16313: Taxanes-Induced Cardiotoxicity in Patients With Breast Cancer: Diagnosis and Prediction. An Echo and Genetic Study
Authors: Maria Florescu, Diana Mihalcea, Stefania Magda, Dan Jinga, Maria Adriana Acasandrei, Eugen Radu, Alexandru Chirca, dragos vinereanu
Journal: Circulation (2014)

Taxanes are powerful drugs, but their use is limited by cardiotoxicity.

Aims: To investigate the mechanisms, and to define predictive models for cardiotoxicity in order to detect the patients at risk for heart failure.

Methods: 40 women with HER2- breast cancer (43±8 y.), were evaluated at baseline, after the 1st cycle, immediately (dose of 540±150 g/m2), and 1 year after the completion of treatment with taxanes, by 4D auto LVQ echo to assess LVEF, and systolic deformation: radial(RS), longitudinal(LS), circumferential(CS), and area strain (AS); arterial stiffness from β index; oxidative stress from Carbonyl Concentration into the Plasma Proteins - CCPP, and genetic variation from genotypes rs28371759, rs2032582, and rs1056836.

Results: Immediately after the treatment, 13 patients (33%) developed cardiotoxicity (group I),recovered 1 year after, while 26 patients (67%)did not fulfill the criteria(group II)(table). After the 1st cycle of taxanes, there were reductions in LS, and AS, persistent even 1year after, but patients from group I had significantly lower AS and LS than group II (table). Arterial stiffness was increased in group I, related to a significant augmentation of oxidative stress (for β: 10.2±3 vs 7.7±3; and for CCPP: 0.500±0.100 vs 0.336±0.104 nmol/mg,p<0.01). Genotype rs1056836 was directly related to the decrease of LVEF after the completion the treatment (r=0.59, p=0.02). AS were inversely related to arterial stiffness and to oxidative stress (r=-0.56 and r=-0.60, p<0.01). A decrease of AS with 18 % after the 1st cycle of taxanes was the most powerful predictor of LVEF reduction after completion of treatment.

Conclusion: Cardiotoxicity induced immediately after completion of treatment, can be diagnosed and predicted by 4D LV deformation. Although recovered after 1 year, early cardiac dysfunction might be related to increased oxidative stress and arterial stiffness, associated with a specific genetic variation.

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Capitation, Managed Care, and Chronic Obstructive Pulmonary Disease
Authors: MARC E. GRASSO, WENDY E. WELLER, THOMAS J. SHAFFER, GREGORY B. DIETTE, GERARD F. ANDERSON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Expenditure and utilization patterns of aged Medicare beneficiaries with chronic obstructive respiratory disease (COPD) (n = 42,472) were compared with all Medicare beneficiaries (n = 1,221,615) using a 5% nationally representative sample of aged Medicare beneficiaries participating in the fee-for-service program in 1992. Per capita expenditures for an aged Medicare beneficiary with COPD were 2.4 times the per capita expenditures for all Medicare beneficiaries. The most expensive 10% of Medicare beneficiaries with COPD accounted for nearly half of total expenditures for this population. Higher comorbidity, as measured by the Deyo-adapted Charlson index, was associated with higher expenditures. For Medicare Part B claims, internal medicine accounted for the largest portion of physician expenditures (14%). Per capita expenditures for pulmonologists were 7.5 times higher for beneficiaries with COPD compared with all Medicare beneficiaries. Results from this study suggest that there is a subgroup of individuals with COPD who are likely to be very expensive during the year. Additional analytic studies are needed to more specifically identify characteristics associated with these individuals. As more Medicare beneficiaries enroll in managed care and as physicians are increasingly being paid on a capitated basis this information will be useful to physicians as they monitor the care provided to patients and assess the financial risks they accept under capitation.