tbuckley/cabot-search huggingface dataset:
Fibrillin-1 Genotype Is Associated With Aortic Stiffness and Disease Severity in Patients With Coronary Artery Disease
Authors: Tanya L. Medley, Timothy J. Cole, Christoph D. Gatzka, William Y.S. Wang, Anthony M. Dart, Bronwyn A. Kingwell
Journal: Circulation (2002)

Elevated pulse pressure is associated strongly with adverse cardiovascular outcome; however, the genetic basis of this condition is unknown. This study examined whether genotypic variation in the extracellular matrix protein fibrillin-1, the Marfan gene, was associated with aortic stiffening and therefore could contribute to cardiovascular risk associated with pulse pressure elevation in coronary disease.Patients (n=145; 113 men), 62+/-9 years of age (mean+/-SD), with angiographically confirmed coronary disease, were studied. Carotid applanation tonometry was used to assess central blood pressures, and in conjunction with Doppler velocimetry, to assess aortic input and characteristic impedance. Fibrillin-1 genotype was characterized by a variable nucleotide tandem repeat and 2 single-nucleotide polymorphisms. The variable nucleotide tandem repeat was a good predictor of underlying haplotypes with 3 genotypes (2-2, 2-4, and 2-3) accounting for 86% of the population. The 2-3 genotype had higher input impedance (P=0.002), characteristic impedance (P=0.005), and carotid pulse pressure (P=0.002) compared with the 2-2 and 2-4 genotypes. Disease severity assessed by previous angioplasties and the number of patients with a stenosis >90% was also greater in the 2-3 genotype. Furthermore, in a multivariate analysis, fibrillin-1 genotype and central pulse pressure were independent of conventional risk factors in determining coronary disease severity. There was no difference in age, sex ratio, body mass index, smoking status, cholesterol level, or medication among the 3 genotypes.Although a causative link has not been shown, these data are consistent with an important role for fibrillin-1 genotype in cardiovascular risk associated with large-artery stiffening and pulse pressure elevation in individuals with coronary disease.
How Does Minor Renal Dysfunction Influence Cardiovascular Risk and the Management of Cardiovascular Disease?
Authors: Tobias Pinkau, Karl F. Hilgers, Roland Veelken, Johannes F. E. Mann
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. This review focuses on the association between mild renal insufficiency (stage 2 and 3 of chronic kidney disease) and cardiovascular disease and discusses therapeutic options. Although the association of chronic renal insufficiency and cardiovascular risk was first shown in patients with end-stage renal disease, even minor renal dysfunction is now established as an independent risk for atherosclerotic cardiovascular disease. The association has been established in patients with a high cardiovascular risk but also in the general population. Treatment with angiotensin-converting enzyme inhibitors and statins can reduce cardiovascular morbidity and mortality in patients with renal insufficiency. Coronary revascularization improves the prognosis in patients with minor renal dysfunction, but there is still an underutilization of coronary revascularization procedures in people with renal insufficiency. The use of coronary stenting has now reduced the incidence of restenosis in these patients, and there is hope that the development of new devices will improve the prognosis in patients with renal insufficiency as well. Nevertheless, people with cardiovascular disease and renal insufficiency die significantly more often than people without renal insufficiency independent of prior successful treatment. Further investigations should focus on the causes of and possible preventive interventions for the staggering cardiovascular risk in the ever-increasing number of people with minor renal dysfunction.
EFFECTS OF SIMULTANEOUS OR PRIOR INFUSION OF SUGARS ON THE FATE OF INFUSED PROTEIN HYDROLYSATES 12
Authors: Halvor N. Christensen, Patricia Bryan Wilber, Barbara A. Coyne, John Herbert Fisher
Journal: Journal of Clinical Investigation (1955)

Glucose usually is included in amino acid solutions for intravenous infusion. This has seemed desirable because the amino acids can spare body protein only when sufficient calories are provided. Although the calories so gained (usually 200 for a liter of hydrolysate) are far from enough for this purpose, they do add to the total and besides they might serve particularly efficiently being presented at the same time as the amino acids. On the other hand Elman and his co-workers (1) have reported improved retention of the nitrogen of a partial hydrolysate when fructose replaced the usual glucose. In explanation these writers suggest that the cellular uptake of the glucose is relatively too late to spare the amino acids optimally, whereas the fructose is metabolized more quickly. The present study was undertaken to compare the effects of glucose and fructose on the fate of the amino acids and peptides of infused hydrolysates. We have found that the presence of either sugar in certain commercial protein hydrolysates interferes with the tissue utilization of the peptides present; the effect increases in the order 10 per cent fructose, 5 per cent glucose, 10 per cent glucose. It is completely avoided if the sugars are added to the hydrolysate sterilely just before infusion or if the sugars are infused in advance of the hydrolysate. Therefore, we conclude that substances which interfere with peptide utilization are formed during autoclaving by interaction between the sugars and constituents of the hydrolysate.
Aggresome Disruption: A Novel Strategy to Enhance Bortezomib-Induced Apoptosis in Pancreatic Cancer Cells
Authors: Steffan T. Nawrocki, Jennifer S. Carew, Maria S. Pino, Ralph A. Highshaw, Robert H.I. Andtbacka, Kenneth Dunner, Ashutosh Pal, William G. Bornmann, Paul J. Chiao, Peng Huang, Henry Xiong, James L. Abbruzzese, David J. McConkey
Journal: Cancer Research (2006)

Abstract The proteasome inhibitor bortezomib (formerly known as PS-341) recently received Food and Drug Administration approval for the treatment of multiple myeloma, and its activity is currently being evaluated in solid tumors. Bortezomib triggers apoptosis in pancreatic cancer cells, but the mechanisms involved have not been fully elucidated. Here, we show that pancreatic cancer cells exposed to bortezomib formed aggregates of ubiquitin-conjugated proteins (“aggresomes”) in vitro and in vivo. Bortezomib-induced aggresome formation was determined to be cytoprotective and could be disrupted using histone deacetylase (HDAC) 6 small interfering RNA or chemical HDAC inhibitors, which resulted in endoplasmic reticulum stress and synergistic levels of apoptosis in vitro and in an orthotopic pancreatic cancer xenograft model in vivo. Interestingly, bortezomib did not induce aggresome formation in immortalized normal human pancreatic epithelial cells in vitro or in murine pancreatic epithelial cells in vivo. In addition, these cells did not undergo apoptosis following treatment with bortezomib, suberoylanilide hydroxamic acid, or the combination, showing tumor selectivity. Taken together, our study shows that inhibition of aggresome formation can strongly potentiate the efficacy of bortezomib and provides the foundation for clinical trials of bortezomib in combination with HDAC inhibitors for the treatment of pancreatic cancer. (Cancer Res 2006; 66(7): 3773-81)
Attenuation of Unfavorable Remodeling by Exercise Training in Postinfarction Patients With Left Ventricular Dysfunction
Authors: Pantaleo Giannuzzi, Pier Luigi Temporelli, Ugo Corrà, Marinella Gattone, Amerigo Giordano, Luigi Tavazzi, for the ELVD Study Group
Journal: Circulation (1997)

Background Exercise is currently recommended for patients after myocardial infarction; however, the effects of regular exercise on the remodeling process remain to be defined. The aim of this multicenter, randomized study was to investigate whether a long-term physical training program influences left ventricular size and function in postinfarction patients with systolic dysfunction. Methods and Results Consecutive patients with &lt;40% ejection fraction after a first Q-wave myocardial infarction were randomly assigned to a 6-month exercise training program (n=39) or control group (n=38). After 6 months, a significant increase in work capacity was observed only in the training group (from 4.462±1.095 to 5.752±1.749 kilopond-meters [Kp-m], P &lt;.01), not in the control group (from 4.375±1.143 to 4.388±1.199 Kp-m), whereas left ventricular volumes had increased in the control group (end-diastolic volume, from 94±26 to 99±27 mL/m 2 , P &lt;.01; end-systolic volume, from 62±20 to 67±23 mL/m 2 , P &lt;.01) but not in the training group (end-diastolic volume, from 93±28 to 92±28 mL/m 2 , P =NS; end-systolic volume, from 61±22 to 57±23 mL/m 2 , P =NS). Conversely, ejection fraction had improved in the training group (from 34±5% to 38±8%, P &lt;.01) but not in the control group (from 34±5% to 33±7%, P =NS). Conclusions In postinfarction patients with systolic dysfunction, long-term exercise training may attenuate the unfavorable remodeling response and even improve ventricular function over time.
GAIP, GIPC and Gαi3 are Concentrated in Endocytic Compartments of Proximal Tubule Cells
Authors: Xiaojing Lou, Tammie McQuistan, Robert A. Orlando, Marilyn Gist Farquhar
Journal: Journal of the American Society of Nephrology (2002)

Megalin is the most abundant endocytic receptor in the proximal tubule epithelium (PTE), where it is concentrated in clathrin-coated pits (CCPs) and vesicles in the brush border region. The heterotrimeric G protein alpha subunit, Galphai3, has also been localized to the brush border region of PTE. By immunofluorescence GIPC and GAIP, components of G protein-mediated signaling pathways, are also concentrated in the brush border region of PTE and are present in megalin-expressing cell lines. By cell fractionation, these signaling molecules cosediment with megalin in brush border and microvillar fractions. GAIP is found by immunoelectron microscopy in CCPs, and GIPC is found in CCPs and apical tubules of endocytic compartments in the renal brush border. In precipitation assays, GST-GIPC specifically binds megalin. The concentration of Galphai3, GIPC, and GAIP with megalin in endocytic compartments of the proximal tubule, where extensive endocytosis occurs, and the interaction between GIPC and the cytoplasmic tail of megalin suggest a model whereby G protein-mediated signaling may regulate megalin's endocytic function and/or trafficking.
Field-based fitness assessment in young people: the ALPHA health-related fitness test battery for children and adolescents
Authors: Jonatan R Ruiz, José Castro-Piñero, Vanesa España-Romero, Enrique G Artero, Francisco B Ortega, Magdalena M Cuenca, David Jimenez-Pavón, Palma Chillón, María J Girela-Rejón, Jesús Mora, Ángel Gutiérrez, Jaana Suni, Michael Sjöström, Manuel J Castillo
Journal: British Journal of Sports Medicine (2010)

The present study summarises the work developed by the ALPHA (Assessing Levels of Physical Activity) study and describes the procedures followed to select the tests included in the ALPHA health-related fitness test battery for children and adolescents. The authors reviewed physical fitness and health in youth findings from cross-sectional studies. The authors also performed three systematic reviews dealing with (1) the predictive validity of health-related fitness, (2) the criterion validity of field-based fitness tests and (3) the reliability of field-based fitness tests in youth. The authors also carried out 11-methodological studies to determine the criterion validity and the reliability of several field-based fitness tests for youth. Finally, the authors performed a study in the school setting to examine the reliability, feasibility and safety of the selected tests. The selected fitness tests were (1) the 20 m shuttle run test to assess cardiorespiratory fitness; (2) the handgrip strength and (3) standing broad jump to assess musculoskeletal fitness, and (4) body mass index, (5) skinfold thickness and (5) waist circumference to assess body composition. When there are time limits, the authors propose the high-priority ALPHA health-related fitness test battery, which comprises all the evidence-based fitness tests except the measurement of the skinfold thickness. The time required to administer this battery to a group of 20 youth by one physical education teacher is less than 2 h. In conclusion, the ALPHA fitness tests battery is valid, reliable, feasible and safe for the assessment of health-related physical fitness in children and adolescents to be used for health monitoring purposes at population level.
Decay-accelerating factor is present on paroxysmal nocturnal hemoglobinuria erythroid progenitors and lost during erythropoiesis in vitro.
Authors: J G Moore, M M Frank, H J Müller-Eberhard, N S Young
Journal: The Journal of Experimental Medicine (1985)

A glycoprotein that regulates the deposition of C3b on the erythrocyte surface, called decay-accelerating factor or DAF, is absent from the red blood cells (RBC) of patients with paroxysmal nocturnal hemoglobinuria (PNH), explaining in part their abnormal sensitivity to complement. We used a specific antiserum to DAF, flow microfluorometry, and clonogenic assays for erythroid progenitor cells to study PNH erythropoiesis in vitro. By fluorescence-activated cell sorter analysis, all RBC from normal individuals are DAF+. In contrast, the RBC of six patients with PNH showed discrete populations of DAF- cells (10-44%; x +/- SEM = 31 +/- 6%). The DAF- RBC population was partly eliminated by prior acidified serum lysis. To determine whether erythropoietic progenitors expressed DAF, bone marrow cells were sorted by flow microfluorometry and the separated DAF+ and DAF- populations then cultured in vitro. In two normal individuals, but also in six patients with PNH, erythroid colonies formed only from cells in the DAF+ fraction. However, a variable proportion of the normoblast progeny of these DAF+ progenitor cells from patients with PNH was DAF-. Individual bursts removed from cultures of PNH bone marrow showed two discrete populations by fluorescence; the majority of normoblasts were DAF-, only 3 of 27 individual bursts had greater than 50% DAF+ cells, and in three patients, DAF- normoblasts averaged 79%. In contrast, the progeny of individual bursts from normal individuals comprised a unimodal DAF+ population. In each PNH patient, one normal burst (greater than 80% DAF+ normoblasts) was detected, possibly reflecting a normal residual population of erythroid progenitors. By the criterion of DAF expression, there was no evidence of separate populations of normal and PNH type progenitor cells. The phenotypically normal erythroid progenitors of PNH bone marrow acquire the PNH characteristics during differentiation in vitro.
Postprandial Vascular Effects of VIAject Compared With Insulin Lispro and Regular Human Insulin in Patients With Type 2 Diabetes
Authors: Thomas Forst, Andreas Pfützner, Frank Flacke, Alan Krasner, Cloth Hohberg, Eda Tarakci, Philip Pichotta, Senait Forst, Solomon Steiner
Journal: Diabetes Care (2009)

OBJECTIVE Recent studies suggested an impact of prandial insulin delivery on postprandial regulation of tissue blood flow. This study compared the effect of VIAject with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Fourteen patients (seven men; aged 61.5 ± 1.8 years; duration of diabetes 6.6 ± 4.6 years; A1C 7.2 ± 0.5% [mean ± SEM]) received a prandial injection of VIAject, human regular insulin, and insulin lispro. At baseline and after a standardized liquid meal test (Ensure Plus), the postprandial increases in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the postprandial effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured. RESULTS Treatment with VIAject resulted in a significant reduction in the peak postprandial generation of ADMA compared with human insulin and insulin lispro (VIAject −27.3 ± 22.6, human insulin 97.7 ± 24.4, and insulin lispro 66.9 ± 33.9 nmol/l; P &amp;lt; 0.05, respectively). The postprandial increases in nitrotyrosine levels were significantly less after VIAject than after human regular insulin (VIAject −0.22 ± 0.17 vs. human insulin 0.25 ± 0.15 μg/ml; P &amp;lt; 0.05), whereas nitrotyrosine after insulin lispro was in between (insulin lispro 0.09 ± 0.07 μg/ml; NS). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after VIAject compared with those after human insulin or insulin lispro (P &amp;lt; 0.05, respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity. CONCLUSIONS Treatment with VIAject reduced postprandial oxidative stress and improved endothelial function compared with human regular insulin or insulin lispro.
Prescription Opioid Misuse, Abuse, and Treatment in the United States: An Update
Authors: Kathleen T. Brady, Jenna L. McCauley, Sudie E. Back
Journal: American Journal of Psychiatry (2015)

Prescription opioid abuse and dependence have escalated rapidly in the United States over the past 20 years, leading to high rates of overdose deaths and a dramatic increase in the number of people seeking treatment for opioid dependence. The authors review the scope of the abuse and overdose epidemic, prescription practices, and the assessment, treatment, and prevention of prescription opioid misuse and dependence.
Design and Analysis of Group-Randomized Trials in Cancer: A Review of Current Practices
Authors: D. M. Murray, S. L. Pals, J. L. Blitstein, C. M. Alfano, J. Lehman
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundPrevious reviews have identified problems in the design and analysis of group-randomized trials in a number of areas. Similar problems may exist in cancer research, but there have been no comprehensive reviews.
Primate Biliary Physiology VIII. THE EFFECT OF PHENOBARBITAL UPON BILE SALT SYNTHESIS AND POOL SIZE, BILIARY LIPID SECRETION, AND BILE COMPOSITION
Authors: Richard N. Redinger, Donald M. Small
Journal: Journal of Clinical Investigation (1973)

Phenobarbital, by inducing liver microsomal enzymes, may affect bile acid synthesis from cholesterol and thus alter the secretion of biliary lipids and the composition of bile. We, therefore, determined the effects of phenobarbital on bile flow, biliary lipid secretion, bile acid synthesis, and bile-acid pool size. Using an experimental preparation that allows controlled interruption of the enterohepatic circulation (1), we administered 5 mg/kg per day of phenobarbital to healthy Rhesus monkeys for 1-2 wk to achieve steady-state conditions. Three animals were studied with an intact enterohepatic circulation and three with a total bile fistula, each animal served as its own control. Total bile flow and secretion of bile salt, phospholipid, and cholesterol were measured every 24 h during steady-state conditions. Further, under conditions of an intact enterohepatic circulation bile-acid synthetic rate was measured in three animals and pool size estimated in two animals during both control and drug treatment periods. Phenobarbital at doses of 5 mg/kg per day increased bile flow 30-50% in all animals (P < 0.001). The increased bile flow resulted from both an increased "bile-salt independent fraction" and an increased bile-salt secretion rate. Phenobarbital significantly increased bile salt (P < 0.01) and phospholipid secretion (P < 0.05) by about 30% but cholesterol secretion was not significantly changed. Consequently, the concentration of cholesterol relative to bile salt and phospholipid was decreased (P < 0.001). Phenobarbital significantly enhanced the maximal rate of bile acid synthesis 25-30% in all three monkeys with total bile fistulas (P < 0.05) and also augmented bile acid synthesis and pool size in animals with intact enterohepatic circulations despite the fact that the rates of bile salt returning to the liver in these animals would have inhibited bile acid synthesis in control animals. Thus, phenobarbital not only increases the maximal rate of bile acid synthesis but also alters the normal control mechanisms by which bile salts returning to the liver inhibit bile salt synthesis. The fact that phenobarbital treatment results in increased synthesis of bile salt and unchanged secretion of cholesterol is consistant with the view that the drug augments conversion of hepatic cholesterol to bile salt. The resulting decrease in relative cholesterol content in bile may have therapeutic implications for cholesterol gallstone therapy.
Effects of succinobucol (AGI-1067) after an acute coronary syndrome: a randomised, double-blind, placebo-controlled trial
Authors: Jean-Claude Tardif, John JV McMurray, Eric Klug, Robert Small, Jennifer Schumi, Jasmine Choi, Jim Cooper, Robert Scott, Eldrin F Lewis, Philippe L L'Allier, Marc A Pfeffer
Journal: The Lancet (2008)
Vasohibin-2 modulates tumor onset in the gastrointestinal tract by normalizing tumor angiogenesis
Authors: Shuji Kitahara, Yasuhiro Suzuki, Masae Morishima, Asuka Yoshii, Sachiko Kikuta, Kazuhiko Shimizu, Shunichi Morikawa, Yasufumi Sato, Taichi Ezaki
Journal: Molecular Cancer (2014)

Vasohibin-2 (VASH2) has been identified as an endogenous and vascular endothelial growth factor (VEGF)-independent angiogenic factor that is highly expressed in tumor cells. In the present study, we aimed to determine whether pre-existing vascular changes can be used to predict tumor transformation as benign or malignant. We sought to characterize microvascular changes and tumor development in the intestinal tract of ApcMin/+ mice and ApcMin/+/Vash2-/- mice.ApcMin/+ mice provide a unique orthotopic model for the development of spontaneous adenomatous polyposis and subsequent carcinomas, a phenomenon termed the adenoma-carcinoma sequence. ApcMin/+ mice were mated with Vash2-/- mice with a mixed C57BL/6 background and the resulting pups were screened for the Min mutation and for the Vash2-/- gene by PCR. Intestinal tumors from ApcMin/+ mice and ApcMin/+/Vash2-/- mice were removed and either frozen or epon-embedded for subsequent analyses. For 3-dimensional imaging using confocal laser-scanning microscopy and transmission electron microscopy, cryosections were made, and immunofluorescent staining for various markers was performed.We found that structural abnormalities in tumor vessels from benign tumors resembled those in malignant tumors. In addition, a novel angiogenic factor, vasohibin-2 (VASH2) protein, was detected around tumor blood vessels in late-stage adenomas and adenocarcinomas, but was absent from early-stage adenomas in ApcMin/+ mice. Tumors used to examine endogenous VASH2 (derived from CMT93 colon carcinomas) were less vascularized in Vash2-/- mice and were more regular than those seen in wild-type (WT) mice. In addition, tumors in Vash2-/- mice were smaller than those in WT mice. Furthermore, cross-breeding of mice homozygous for a deletion of Vash2 with mice heterozygous for the APC mutation resulted in animals that showed a significant decrease in the number of polyps in the small intestine.We propose that VASH2 may modulate the onset of tumors in the gastrointestinal tract by regulating tumor angiogenesis.