tbuckley/cabot-search huggingface dataset:
Anabolic Actions of Parathyroid Hormone on Bone*
Authors: DAVID W. DEMPSTER, FELICIA COSMAN, MAY PARISIEN, VICTOR SHEN, ROBERT LINDSAY
Journal: Endocrine Reviews (1993)

PHYSICIANS have traditionally considered PTH to be an agent that is catabolic to the skeleton. However, as early as 60 yr ago, Albright and his colleagues (1) and later Selye (2) noted that the peptide extract could also be anabolic to the skeleton, producing increases in bone tissue in animals. The potential for an agent that can increase bone mass and hence reverse the skeletal defect in patients with osteoporosis is great, particularly if in doing so it also repairs microarchitectural damage. The agents currently available in the United States for treatment of osteoporosis, estrogens and salmon calcitonin, primarily stabilize bone mass and prevent further loss of bone, although a transient small increment in mass is often reported, particularly in patients with elevated levels of bone remodeling. This increase is not a true anabolic effect but is related to the temporal effects on turnover in which resorption declines initially followed by a reduction in formation that may take several months. Fluoride, in contrast, does increase bone mass by a true anabolic action, but there is controversy about the quality of the bone formed. Two recent controlled studies failed to find a reduction in fracture recurrence (3, 4), although the dose may have been excessive, and consequently, fluoride is currently not approved for treatment of osteoporosis in the United States. Thus, if PTH is capable of improving bone mass and quality, the peptide will have a potential therapeutic role in osteoporosis. This review summarizes the data available to date, starting at the cellular level.
Abstract 4628: PBISe, an iNOS/Akt inhibitor for colon cancer chemoprevention
Authors: Dhimant H. Desai, Rosalyn Irby, Cesar Aliaga, Shantu G. Amin
Journal: Cancer Research (2011)

Abstract Colorectal cancer (CRC) is one of the leading causes of premature death in people worldwide. Conversion of normal colonic cells to malignant lesions requires several steps and therefore often proceeds over considerable time periods, on average, 10-15 years, thus providing a window of opportunity for effective intervention and prevention. In 2010 it was estimated that in USA alone about 150,000 people will be diagnosed with colorectal cancer and that about 50,000 people will die of the disease. Today, there is handful of truly effective drugs for colon cancer is available for the patients giving a variety of chemotherapy cocktails. Preventive therapies are promising approach for treatment of cancer, and it has a potential to be a major component of colorectal cancer control. Inducible nitric oxide synthase (iNOS) deregulation and PI3K pathways are such events occurring in colon cancer development. Currently known iNOS inhibitors, such as, S,S’-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBIT), require high concentration for clinical efficacy in colon cancer prevention causing systemic toxicity. It is known in the literature that by replacement of sulfur with selenium in the molecule provide a higher inhibitory potency to the compound. Therefore, to develop more potent agent effective at significantly lower concentration, a novel isosteric selenium analog, namely; Se,Se’-1,4-phenylene-bis(1,2-ethanediyl)bis-isoselenourea (PBISe) was developed. Preliminary investigation from our laboratory indicates that PBISe is 25 fold more potent than PBIT in four colon cancer cell lines in MTS assay. Western blot analysis showed decrease pAkt and Akt2 levels, and downstream pPRAS40 levels, and increase in cleaved PARP an apoptosis markers that are specific for Colon cancer. The results from our investigation on maximum tolerated dose (MTD) in FBV mice and male F344 rat when feed with PBISe in a diet as well as tumorigenicity in male (heterozygous) C57BL/6J-APCmin mice and in vitro studies will be discussed. These investigations are highly significant providing insight into the chemoprevention potential and mechanisms based development of PBISe that will inhibit colon cancer. This study was supported by NCI grant CA137763 (DD). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4628. doi:10.1158/1538-7445.AM2011-4628
Double-Blind Comparison of Sertraline, Imipramine, and Placebo in the Treatment of Dysthymia: Effects on Personality
Authors: D J Hellerstein, J H Kocsis, D Chapman, J W Stewart, W Harrison
Journal: American Journal of Psychiatry (2000)

Although previous studies have shown that dysthymia, or chronic depression, commonly responds to antidepressant medications (with improvements in depressive symptoms and psychosocial functioning), there have been no systematic studies of the impact of antidepressant treatment on personality variables in patients with this disorder.In a multicenter study, 410 patients with early-onset primary dysthymia were treated in a randomized prospective fashion with sertraline, imipramine, or placebo. The data were analyzed in terms of the subjects' scores on the Tridimensional Personality Questionnaire, a 100-item self-report instrument that measures four temperamental dimensions: harm avoidance, reward dependence, novelty seeking, and persistence.At baseline, the harm avoidance scores of the dysthymic subjects were approximately 1.5 standard deviations higher than those of a previously reported community sample. After treatment, there was a significant decrease in harm avoidance scores, with no significant between-group differences. Remission of dysthymia was associated with significantly greater improvement in harm avoidance, with the greatest numerical change found in the patients treated with sertraline. Subjects' Tridimensional Personality Questionnaire scores were correlated at a 0.50 level with the Social Adjustment Scale both pre- and posttreatment, suggesting that a high degree of harm avoidance may be associated with poor social functioning.Before treatment, chronically depressed patients demonstrate an abnormality in temperament, as measured by elevated degrees of harm avoidance. Remission of dysthymia is associated with improvement in this aspect of temperament.
Effect of cimetidine on enzyme inactivation, bile acid precipitation, and lipid solubilisation in pancreatic steatorrhoea due to cystic fibrosis.
Authors: P L Zentler-Munro, D R Fine, J C Batten, T C Northfield
Journal: Gut (1985)

In pancreatic steatorrhoea, both pH-dependent bile acid precipitation and enzyme inactivation may limit the efficacy of pancreatic enzyme supplements and both may be preventable by addition of cimetidine. To separate these effects we compared postprandial jejunal aspirate from eight adults with steatorrhoea due to cystic fibrosis on three randomised treatment regimens (pancreatin, cimetidine, and both together). We also compared the results with those of previous studies of patients on no treatment, and of healthy subjects. On pancreatin 60% of the test meal entered the jejunum at pH less than 5 compared with 17% in health. Lipase concentration and lipolysis increased over the values on no treatment (14.2 vs 4.4 U/l, p less than 0.01; 16% vs 11%, p less than 0.02) but bile acid precipitation was not reduced (38% vs 27%, NS), and aqueous-phase lipid concentration decreased (6.7 vs 8.6 mM/l, p less than 0.05). On cimetidine, bile acid precipitation fell (19% vs 38%, p less than 0.05); although lipase concentration and lipolysis were lower than on pancreatin (4.8 U/l vs 14.2 U/l, p less than 0.01; 9% vs 16%, p less than 0.01) lipid solubilisation increased (8.8 vs 6.7 mM/l, p less than 0.05). On the combination, there was a marked improvement (p less than 0.02) in lipid solubilisation (18.3 mM/l), reflecting the improvement both in lipase (38.4 U/l) and lipolysis (24%), and in bile acid precipitation (5.6%). We conclude that the efficacy of pancreatin is limited by pH-dependent bile acid precipitation in addition to enzyme inactivation. The action of cimetidine in improving the efficacy of pancreatin depends on prevention of both these effects.
Inconsistent results or inconsistent methods? A plea for standardisation of biomarker sampling in mesothelioma studies
Authors: K. G. Blyth
Journal: Thorax (2014)

Reproducibility is a quality that all biomarkers must demonstrate before entering the clinical arena. In October's issue of Thorax , Creaney et al 1 reported important diagnostic performance data regarding fibulin-3 in malignant pleural mesothelioma (MPM). Their results (plasma area under the curve (AUC) 0.671, sensitivity 21%) are remarkably discordant with those reported by Pass et al ,2 using the same assay in a similarly designed study (plasma AUC 0.974–0.997, sensitivity 97%). Although some discordance is expected, this pattern is common in the MPM biomarker …
THE ENHANCING EFFECT OF URETHANE ON THE SEVERITY OF INFECTION WITH PNEUMONIA VIRUS OF MICE (PVM)
Authors: George S. Mirick, J. MacLean Smith, Charles I. Leftwich, William B. Leftwich
Journal: The Journal of Experimental Medicine (1952)

Urethane, given parenterally or orally to mice, increased the severity of PVM infection. Not only were the lesions more extensive but mice could be infected with smaller inocula of virus and the multiplication of virus in the lung was enhanced. There was atrophy of lymphoid tissues but no suppression was noted of antibody formation. No relation could be found between PVM infection and the development of pulmonary adenomas in mice.
Rat Spleen Dendritic Cells Express Natural Killer Cell Receptor Protein 1 (NKR-P1) and Have Cytotoxic Activity to Select Targets via a Ca2+-dependent Mechanism
Authors: Régis Josien, Michèle Heslan, Jean-Paul Soulillou, Maria-Cristina Cuturi
Journal: The Journal of Experimental Medicine (1997)

Dendritic cells (DC) are a subset of leukocytes whose major function is antigen presentation. We investigated the phenotype and function of enriched (95–98.5%) rat DC. We show that both spleen and thymus DC express the natural killer cell receptor protein 1 (NKR-P1) as a disulfide linked homodimer of 60 kD. Freshly isolated DC express a low level of NKR-P1, which is strongly upregulated after overnight culture. Spleen, but not thymus DC, were able to kill the NK-sensitive YAC-1 cell line in vitro, and since this killing was Ca2+ dependent, a Fas ligand–Fas interaction was probably not involved. Besides their potent antigen-presenting function, DC can thus be cytotoxic for some tumor targets.
Risk Taking and the Adolescent Reward System: A Potential Common Link to Substance Abuse
Authors: Sophia Schneider, Jan Peters, Uli Bromberg, Stefanie Brassen, Stephan F. Miedl, Tobias Banaschewski, Gareth J. Barker, Patricia Conrod, Herta Flor, Hugh Garavan, Andreas Heinz, Bernd Ittermann, Mark Lathrop, Eva Loth, Karl Mann, Jean-Luc Martinot, Frauke Nees, Tomas Paus, Marcella Rietschel, Trevor W. Robbins, Michael N. Smolka, Rainer Spanagel, Andreas Ströhle, Maren Struve, Gunter Schumann, Christian Büchel
Journal: American Journal of Psychiatry (2011)

Increased risk-taking behavior has been associated with addiction, a disorder also linked to abnormalities in reward processing. Specifically, an attenuated response of reward-related areas (e.g., the ventral striatum) to nondrug reward cues has been reported in addiction. One unanswered question is whether risk-taking preference is associated with striatal reward processing in the absence of substance abuse.Functional and structural MRI was performed in 266 healthy young adolescents and in 31 adolescents reporting potentially problematic substance use. Activation during reward anticipation (using the monetary incentive delay task) and to gray matter density were measured. Risk-taking bias was assessed by the Cambridge Gamble Task.With increasing risk-taking bias, the ventral striatum showed decreased activation bilaterally during reward anticipation. Voxel-based morphometry showed that greater risk-taking bias was also associated with and partially mediated by lower gray matter density in the same structure. The decreased activation was also observed when participants with virtually any substance use were excluded. The group with potentially problematic substance use showed greater risk taking as well as lower striatal activation relative to matched comparison subjects from the main sample.Risk taking and functional and structural properties of the reward system in adolescents are strongly linked prior to a possible onset of substance abuse, emphasizing their potential role in the predisposition to drug abuse.
Comparison of fatigue and sleep quality between COPD and healthy subjects
Authors: Irene Torres-Sánchez, Marie Carmen Valenza, Maröa José Flores-Barba, Gregory Reychler
Journal: European Respiratory Journal (2013)

Sleep quality and fatigue are prevalent symptoms in COPD. Numerous studies have been focused on fatigue previously but no one has observed the relationship between sleep quality and fatigue.

Fatigue was measured with Piper fatigue scale (PFS) and sleep quality was assessed with Pittsburgh sleep quality index (PSQI).

Finally, 23 COPD patients were matched with comparable 25 healthy controls.

COPD group shown a significantly worse score sleep quality (9.88±4.43 vs 5.85±3.15, p<0.001) than control group. COPD group showed significative worse scores (p<0.05) in cognitive and affective subscales Piper Fatigue Scale.

View this table:

Fatigue and sleep quality in COPD patients and healthy subjects





In conclusion, sleep and fatigue are worse in COPD than in comparable controls. More studies are needed to improve the knowledge of this association.
Altered synthesis and intracellular transport of proteoglycans by cyst-derived cells from human polycystic kidneys.
Authors: H Jin, F A Carone, S Nakamura, Z Z Liu, Y S Kanwar
Journal: Journal of the American Society of Nephrology (1992)

Employing in vitro pulse-chase techniques, we investigated the de novo synthesis and the kinetics of intracellular transport and extracellular matrix incorporation of proteoglycans (PG) by normal human renal epithelial cell and by epithelial cells isolated from cysts of autosomal dominant kidneys (ADPKD). Cell monolayers were pulsed either with (3H)leucine for 15 min and chased for seven intervals between 15 and 270 min or with (35S)sulfate for 150 min and chased for a single interval of 120 min. Total proteins and PG were isolated from cell, media, and matrix fractions and characterized by Sepharose CL-6B and DEAE-Sephacel chromatographies. ADPKD and NK cells synthesized comparable amounts of total proteins; however, the de novo synthesis of PG by ADPKD cells was significantly reduced. ADPKD versus NK cells exhibited a substantial delay in the cellular transport and extracellular release of de novo synthesized PG, indicating an impairment at the level of the Golgi complex and/or secretory vacuoles. PG synthesized by ADPKD versus NK cells had decreased charge density characteristics, probably due to a posttranslational defect in the sulfation of the PG glycosaminoglycan chains. ADPKD versus NK cells synthesized PG of higher molecular weight and had an increased proportion of chondroitin sulfate PG versus heparan sulfate PG. Collectively, these findings suggest a defect in the synthesis and intracellular transport of sulfated PG in human ADPKD cells.
Pannexin1 Regulates α1-Adrenergic Receptor– Mediated Vasoconstriction
Authors: Marie Billaud, Alexander W. Lohman, Adam C. Straub, Robin Looft-Wilson, Scott R. Johnstone, Christina A. Araj, Angela K. Best, Faraaz B. Chekeni, Kodi S. Ravichandran, Silvia Penuela, Dale W. Laird, Brant E. Isakson
Journal: Circulation Research (2011)

The coordination of vascular smooth muscle cell constriction plays an important role in vascular function, such as regulation of blood pressure; however, the mechanism responsible for vascular smooth muscle cell communication is not clear in the resistance vasculature. Pannexins (Panx) are purine-releasing channels permeable to the vasoconstrictor ATP and thus may play a role in the coordination of vascular smooth muscle cell constriction.We investigated the role of pannexins in phenylephrine- and KCl-mediated constriction of resistance arteries.Western blot, immunohistochemistry, and immunogold labeling coupled to scanning and transmission electron microscopy revealed the presence of Panx1 but not Panx2 or Panx3 in thoracodorsal resistance arteries. Functionally, the contractile response of pressurized thoracodorsal resistance arteries to phenylephrine was decreased significantly by multiple Panx inhibitors (mefloquine, probenecid, and (10)Panx1), ectonucleotidase (apyrase), and purinergic receptor inhibitors (suramin and reactive blue-2). Electroporation of thoracodorsal resistance arteries with either Panx1-green fluorescent protein or Panx1 small interfering RNA showed enhanced and decreased constriction, respectively, in response to phenylephrine. Lastly, the Panx inhibitors did not alter constriction in response to KCl. This result is consistent with coimmunoprecipitation experiments from thoracodorsal resistance arteries, which suggested an association between Panx1 and α1D-adrenergic receptor.Our data demonstrate for the first time a key role for Panx1 in resistance arteries by contributing to the coordination of vascular smooth muscle cell constriction and possibly to the regulation of blood pressure.
Biomechanics laboratory-based prediction algorithm to identify female athletes with high knee loads that increase risk of ACL injury
Authors: Gregory D Myer, Kevin R Ford, Jane Khoury, Paul Succop, Timothy E Hewett
Journal: British Journal of Sports Medicine (2010)

Knee abduction moment (KAM) during landing predicts non-contact anterior cruciate ligament (ACL) injury risk with high sensitivity and specificity in female athletes. The purpose of this study was to employ sensitive laboratory (lab-based) tools to determine predictive mechanisms that underlie increased KAM during landing.
Vascular responses to activated leukocytes after regression of atherosclerosis.
Authors: R C Padgett, D D Heistad, A Mügge, M L Armstrong, D J Piegors, J A Lopez
Journal: Circulation Research (1992)

Activation of leukocytes in vivo produces marked constriction of large arteries in atherosclerotic, but not in normal, monkeys. We tested the hypotheses that vasoconstrictor responses to activated leukocytes in vivo may be abnormal during hypercholesterolemia before the development of atherosclerotic lesions and that responses may return to normal after the regression of atherosclerosis. Leukocytes were activated by injection of the chemotactic peptide formyl-methionine-leucine-phenylalanine (fMLP) into the blood-perfused hind limb of four groups of cynomolgus monkeys: monkeys fed a normal diet (normal group, n = 18), monkeys fed an atherogenic diet for 3-4 months (hypercholesterolemic group, n = 6), monkeys fed an atherogenic diet for 20 months (atherosclerotic group, n = 19), and monkeys fed an atherogenic diet for 18 months, followed by a normal diet for 20 months (regression group, n = 14). Baseline resistance of large arteries was 1.5 +/- 0.2 (mean +/- SEM), 2.0 +/- 0.6, 3.5 +/- 0.4 (p less than 0.05 versus normal), and 1.7 +/- 0.2 mm Hg/ml/min per 100 g tissue for the normal, hypercholesterolemic, atherosclerotic, and regression groups, respectively. Injection of fMLP did not change resistance of large arteries in normal or hypercholesterolemic monkeys. Injection of fMLP increased resistance of large arteries by 3.0 +/- 0.7 mm Hg/ml/min per 100 g tissue in atherosclerotic monkeys and by 1.3 +/- 0.4 mm Hg/ml/min per 100 g tissue in regression monkeys (p less than 0.05 versus atherosclerotic and normal). Thus, abnormal vasoconstriction in response to activation of leukocytes persists, but to a lesser extent, after regression. In contrast, vasoconstrictor responses to serotonin, which were potentiated in atherosclerotic monkeys, were normal after regression.(ABSTRACT TRUNCATED AT 250 WORDS)
Decreased number of activated macrophages in gallbladder muscle layer of cholesterol gallstone patients following ursodeoxycholic acid
Authors: M P L Guarino, S Carotti, S Morini, G Perrone, J Behar, A Altomare, R Alloni, R Caviglia, S Emerenziani, C Rabitti, M Cicala
Journal: Gut (2008)

We recently reported that, in symptomatic cholesterol gallstone patients, ursodeoxycholic acid (UDCA) improves gallbladder (GB) muscle contractility and decreases the biochemical parameters of oxidative stress and inflammation.1 UDCA also antagonises the hydrophobic bile acid damage to the liver by preventing hydrophobic bile acid-induced stimulation of macrophage oxidative processes.2 3 Macrophages also play a dominant role in the inflammatory and oxidative response in other conditions associated with impairment of intestinal motility, such as post-operative ileus.4–6 Following these findings, we carried out additional studies aimed at examining: the presence of macrophage infiltration and cyclooxygenase-2 (COX-2) expression in the GB muscle layer and the effect of short-term UDCA administration.

From February 2004 to August 2007, …
Targeting Wnt Signaling: Can We Safely Eradicate Cancer Stem Cells?
Authors: Fumi Takahashi-Yanaga, Michael Kahn
Journal: Clinical Cancer Research (2010)

The Wnt signaling pathways have been conserved throughout evolution and regulate cell proliferation, morphology, motility, and fate during embryonic development. These pathways also play important roles throughout adult life to maintain homeostasis of tissues including skin, blood, intestine, and brain by regulating somatic stem cells and their niches. Aberrant regulation of the Wnt pathway leads to neoplastic proliferation in these same tissues. It has been suggested that Wnt signaling is also involved in the regulation of cancer stem cells (CSC), because there are many similarities in the signaling pathways that regulate normal adult stem cells and CSC. In this Perspective, we have focused on the Wnt/beta-catenin signaling pathway, which is the most intensively studied and best characterized Wnt signaling pathway. We provide an overview on the function of the Wnt/beta-catenin signaling pathway in CSC, and the possibility of the development of novel therapeutics to target this pathway.
Human Peroxiredoxin PrxI Is an Orthologue of Yeast Tsa1, Capable of Suppressing Genome Instability in <i>Saccharomyces cerevisiae</i>
Authors: Ismail Iraqui, Gérard Faye, Sandrine Ragu, Amélie Masurel-Heneman, Richard D. Kolodner, Meng-Er Huang
Journal: Cancer Research (2008)

Abstract The peroxiredoxins (Prx) are conserved antioxidant proteins that use cysteine as the primary site of oxidation during the reduction of peroxides. Many organisms have more than one isoform of Prx. Deletion of TSA1, one of five Prxs in yeast Saccharomyces cerevisiae, results in accumulation of a broad spectrum of mutations including gross chromosomal rearrangements. Deletion of TSA1 is synthetically lethal with mutations in RAD6 and several key genes involved in DNA double-strand break repair. Here, we have examined the function of human PrxI and PrxII, which share a high degree of sequence identity with Tsa1, by expressing them in S. cerevisiae cells under the control of the native TSA1 promoter. We found that expression of PrxI, but not PrxII, was capable of complementing a tsa1Δ mutant for a variety of defects including genome instability, the synthetic lethality observed in rad6Δ tsa1Δ and rad51Δ tsa1Δ double mutants, and mutagen sensitivity. Moreover, expression of either Tsa1 or PrxI prevented Bax-induced cell death. These data indicate that PrxI is an orthologue of Tsa1. PrxI and Tsa1 seem to act on the same substrates in vivo and share similar mechanisms of function. The observation that PrxI is involved in suppressing genome instability and protecting against cell death potentially provides a better understanding of the consequences of PrxI dysfunction in human cells. The S. cerevisiae system described here could provide a sensitive tool to uncover the mechanisms that underlie the function of human Prxs. [Cancer Res 2008;68(4):1055–63]