tbuckley/cabot-search huggingface dataset:
REGULATION OF MILK PROTEIN GENE EXPRESSION
Authors: Jeffrey M. Rosen, Shannon L. Wyszomierski, Darryl Hadsell
Journal: Annual Review of Nutrition (1999)

▪ Abstract Studies using both transgenic mice and transfected mammary epithelial cells have established that composite response elements containing multiple binding sites for several transcription factors mediate the hormonal and developmental regulation of milk protein gene expression. Activation of signal transduction pathways by lactogenic hormones and cell-substratum interactions activate transcription factors and change chromatin structure and milk protein gene expression. The casein promoters have binding sites for signal transducers and activators of transcription 5, Yin Yang 1, CCAAT/enhancer binding protein, and the glucocorticoid receptor. The whey protein gene promoters have binding sites for nuclear factor I, as well as the glucocorticoid receptor and the signal transducers and activators of transcription 5. The functional importance of some of these factors in mammary gland development and milk protein gene expression has been elucidated by studying mice in which some of these factors have been deleted.
Improvement of plasma lipoprotein profiles during high-flux dialysis.
Authors: D S Seres, G W Strain, S A Hashim, I J Goldberg, N W Levin
Journal: Journal of the American Society of Nephrology (1993)

Patients undergoing maintenance hemodialysis therapy have increased mortality due to cardiovascular disease. One possible etiologic factor for this increased mortality is the lipid abnormalities associated with chronic renal failure. These include elevated triglyceride (TG) and decreased high-density lipoprotein (HDL) concentrations. Lipoprotein profiles of patients undergoing chronic hemodialysis with either saponified cellulose ester (CE) (N = 9) or polysulfone (PS) high-flux dialysis membranes (N = 10) were compared. Patients in each group received similar amounts of heparin during the dialysis. CE-dialyzed patients showed no alteration in serum TG, HDL, low-density lipoprotein, or total cholesterol when predialysis and postdialysis values were compared. PS patients, on the other hand, had a significant decrease in TG concentrations (P < 0.01) as well as a significant rise in HDL (P < 0.01). These changes might signify activation of lipoprotein lipase (LPL) during dialysis. LPL activity in PS sera was significantly greater than LPL in CE sera. Moreover, sera from PS patients inhibited LPL much less than did sera from CE patients. These findings suggest that a circulating substance not dialyzable with cellulosic membranes inhibits LPL in uremic subjects and is removed during dialysis with a PS membrane. Alternatively, the greater biocompatibility of PS may produce less LPL inhibitory cytokines during dialysis. The improvement of lipoprotein profiles in patients receiving dialysis with PS membranes may, in the long term, lead to less morbidity and mortality from atherosclerotic disease.
THE ROLE OF THE KIDNEY IN THE CATABOLISM OF BENCE JONES PROTEINS AND IMMUNOGLOBULIN FRAGMENTS
Authors: R. Dean Wochner, Warren Strober, Thomas A. Waldmann
Journal: The Journal of Experimental Medicine (1967)

The role of the kidney in the catabolism of Bence Jones proteins, intact IgG molecules, and isolated L chains, Fab and Fc fragments of IgG, was studied. The proteins were purified, radioiodinated, and their survival times measured in nephrectomized, ureter-severed, and control mice. Active endogenous catabolism was the major factor in overall Bence Jones metabolism since excretion as proteinuria accounted for less than 25% of the total metabolism. The survival times of λ- and κ-type human Bence Jones proteins and the Bence Jones protein produced by mice with MPC-2 plasma cell tumor were exceedingly short in both unoperated and ureter-severed mice, with 50% of the injected protein catabolized in from 0.8–1.6 hr. In contrast, the survival of Bence Jones protein was markedly prolonged in nephrectomized animals, with 50% of the injected dose catabolized in from 9 to 17 hr. This ten-fold decrease in catabolic rate indicates that the kidneys are the major site of breakdown of Bence Jones proteins. Similar studies with other proteins indicated that the kidneys are also the major site for catabolism of isolated L chains but not of intact IgG molecules. The Fc immunoglobulin fragment was not catabolized and the Fab fragment only partially catabolized by the kidney. When ureter-severed animals were allowed to develop advanced uremia before being studied, the survival of Bence Jones protein was greatly prolonged, indicating that the catabolic process is impaired in the presence of uremia. The nature of this renal catabolism remains unknown. These observations suggest that the Bence Jones proteins and L chains observed in the urine of patients may reflect only a small fraction of such molecules synthesized by these patients. Furthermore, they provide an explanation for the prolongation of Bence Jones protein survival and the development of Bence Jones proteinemia observed in subjects with multiple myeloma and impaired renal function.
Macrolides and pneumonia
Authors: Jeremy Stuart Brown, Adam T Hill
Journal: Thorax (2013)

Community acquired pneumonia (CAP) is increasing in incidence, and is presently responsible for about 1% of emergency medical admissions with an associated mortality of between 5% and 24%. Improving the outcome of CAP is, therefore, a major health priority, but what is the best method to do this? Many audits have shown poor adherence to national guidelines for the management of CAP, with the inference that this may negatively affect outcome. One example of poor compliance is with empirical antibiotic therapy, the mainstay of treatment for most patients. Major guidelines for CAP advise that patients admitted to hospital with moderate and severe CAP should be treated with a combination of a β lactam and a macrolide,1 yet large national audit datasets show that over a third of patients may be treated with β lactams alone.2 ,3 If the poor compliance with CAP guidelines affects outcome this would have serious implications for care of these patients and provide an obvious mechanism to improve their mortality. Conversely, using dual therapy when monotherapy is adequate will incur unnecessary additional cost, an increased risk of complications, and potentially encourage antibiotic resistance among commensal organisms.

The guidance to use dual β lactam and macrolide antibiotics for empirical therapy of CAP for hospitalised patients moderate and severe CAP is based on microbiology data showing around 20% of CAP is caused by ‘atypical’ organisms ( Mycoplasma pneumoniae , Chlamydophila pneumoniae and Legionella pneumophila ); these do not respond to β lactams but are sensitive to macrolides. However, there are almost no controlled trial data on the relative efficacy of these regimens to support the guideline recommendations. In this context, Rodrigo et al have used data from the British Thoracic Society …
Novel magnetic/ultrasound focusing system enhances nanoparticle drug delivery for glioma treatment
Authors: P.-Y. Chen, H.-L. Liu, M.-Y. Hua, H.-W. Yang, C.-Y. Huang, P.-C. Chu, L.-A. Lyu, I.-C. Tseng, L.-Y. Feng, H.-C. Tsai, S.-M. Chen, Y.-J. Lu, J.-J. Wang, T.-C. Yen, Y.-H. Ma, T. Wu, J.-P. Chen, J.-I. Chuang, J.-W. Shin, C. Hsueh, K.-C. Wei
Journal: Neuro-Oncology (2010)

Malignant glioma is a common and severe primary brain tumor with a high recurrence rate and an extremely high mortality rate within 2 years of diagnosis, even when surgical, radiological, and chemotherapeutic interventions are applied. Intravenously administered drugs have limited use because of their adverse systemic effects and poor blood–brain barrier penetration. Here, we combine 2 methods to increase drug delivery to brain tumors. Focused ultrasound transiently permeabilizes the blood–brain barrier, increasing passive diffusion. Subsequent application of an external magnetic field then actively enhances localization of a chemotherapeutic agent immobilized on a novel magnetic nanoparticle. Combining these techniques significantly improved the delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea to rodent gliomas. Furthermore, the physicochemical properties of the nanoparticles allowed their delivery to be monitored by magnetic resonance imaging (MRI). The resulting suppression of tumor progression without damaging the normal regions of the brain was verified by MRI and histological examination. This noninvasive, reversible technique promises to provide a more effective and tolerable means of tumor treatment, with lower therapeutic doses and concurrent clinical monitoring.
M<scp>ECHANISM AND</scp> R<scp>EGULATION OF</scp> S<scp>ELENOPROTEIN</scp> S<scp>YNTHESIS</scp>
Authors: Donna M. Driscoll, Paul R. Copeland
Journal: Annual Review of Nutrition (2003)

▪ Abstract Selenium is an essential trace element that is incorporated into proteins as selenocysteine (Sec), the twenty-first amino acid. Sec is encoded by a UGA codon in the selenoprotein mRNA. The decoding of UGA as Sec requires the reprogramming of translation because UGA is normally read as a stop codon. The translation of selenoprotein mRNAs requires cis-acting sequences in the mRNA and novel trans-acting factors dedicated to Sec incorporation. Selenoprotein synthesis in vivo is highly selenium-dependent, and there is a hierarchy of selenoprotein expression in mammals when selenium is limiting. This review describes emerging themes from studies on the mechanism, kinetics, and efficiency of Sec insertion in prokaryotes. Recent developments that provide mechanistic insight into how the eukaryotic ribosome distinguishes between UGA/Sec and UGA/stop codons are discussed. The efficiency and regulation of mammalian selenoprotein synthesis are considered in the context of current models for Sec insertion.
The role of microRNAs in bone remodeling
Authors: Dian Jing, Jin Hao, Yu Shen, Ge Tang, Mei-Le Li, Shi-Hu Huang, Zhi-He Zhao
Journal: International Journal of Oral Science (2015)

Bone remodeling is balanced by bone formation and bone resorption as well as by alterations in the quantities and functions of seed cells, leading to either the maintenance or deterioration of bone status. The existing evidence indicates that microRNAs (miRNAs), known as a family of short non-coding RNAs, are the key post-transcriptional repressors of gene expression, and growing numbers of novel miRNAs have been verified to play vital roles in the regulation of osteogenesis, osteoclastogenesis, and adipogenesis, revealing how they interact with signaling molecules to control these processes. This review summarizes the current knowledge of the roles of miRNAs in regulating bone remodeling as well as novel applications for miRNAs in biomaterials for therapeutic purposes.
Waiting for radiotherapy: New initiatives may transform service
Authors: Robin D Hunter
Journal: BMJ (2006)

Editor—Dodwell and Crellin analyse the problems of the current radiotherapy service in the United Kingdom.1 Some important initiatives are under way in England and Scotland to make the service workload sensitive.

Faced, in 2003, with Royal College of Radiologists audits2 3 and an Audit Commission report4 identifying a serious deterioration in waiting times for radiotherapy over the previous five years, the Department of Health in England created a standing multidisciplinary national radiotherapy …
The association between erosive hand osteoarthritis and subchondral bone attrition of the knee: the Framingham Osteoarthritis Study
Authors: Ida Kristin Haugen, David T Felson, Martin Englund, Ke Wang, Piran Aliabadi, Ali Guermazi, Frank W Roemer, Tuhina Neogi
Journal: Annals of the Rheumatic Diseases (2012)

To examine whether erosive hand osteoarthritis (OA) is associated with knee subchondral bone attrition (SBA) and systemic bone mineral density (BMD).Associations of MRI-defined knee SBA with radiographic erosive hand OA were evaluated in 1253 Framingham participants using logistic regression with generalised estimating equations. We also examined the association between the number of erosive OA finger joints and SBA adjusted for the number of non-erosive OA finger joints. Associations between erosive hand OA and femoral neck BMD were explored in 2236 participants with linear regression. Analyses were adjusted for age, sex and body mass index.Participants with erosive hand OA had increased odds of knee SBA (OR=1.60, 95% CI 1.07 to 2.38). The relation between the number of erosive OA finger joints and SBA became non-significant when adjusted for the number of non-erosive OA joints as a proxy for the burden of disease. There was a non-significant trend towards higher BMD in erosive hand OA compared with participants without hand OA.Erosive hand OA was associated with knee SBA, but the relation might be best explained by a heightened burden of disease. No significant relation of erosive hand OA with BMD was found.
Comment on: Gaillard et al. HDL Dysfunctionality (Paraoxonase) Is Worse in Nondiabetic, Postmenopausal African American Than in White Women. Diabetes Care 2011;34:e19
Authors: Alena Viktorinova, Sona Kinova
Journal: Diabetes Care (2011)

We read with interest the recent study by Gaillard et al. (1) focused on relationships between paraoxonase (PON1) activity and oxidized LDL and cardiovascular disease (CVD) risk factors in nondiabetic, postmenopausal women. Higher CVD mortality and morbidity in the presence of higher HDL cholesterol is a frequent occurrence in African American women compared with white women. The authors reported the ethnic HDL–related dysfunction (as measured by PON1) in nondiabetic women. They concluded that this paradox may be caused by enhanced LDL oxidation associated with HDL dysfunctionality (lower activity of PON1) in a group …
Natural course of the impairment of endothelium-dependent relaxations after balloon endothelium removal in porcine coronary arteries. Possible dysfunction of a pertussis toxin-sensitive G protein.
Authors: H Shimokawa, N A Flavahan, P M Vanhoutte
Journal: Circulation Research (1989)

The purposes of the present study were to examine the natural course of the impairment of endothelium-dependent relaxations during a regeneration and tissue repair process after balloon endothelium removal and to elucidate the cellular mechanism(s) underlying it. Twenty-three male Yorkshire pigs underwent balloon endothelium removal along the proximal portion of either the left anterior descending or circumflex coronary artery and were then maintained on a regular chow for 4, 8, 16, or 24 weeks. Endothelium-dependent responses were examined in vitro in rings taken from the control and previously denuded arteries studied in parallel. Morphometric analysis revealed that intimal thickening developed only at the previously denuded area. In the previously denuded arteries with regenerated endothelium, the endothelium-dependent relaxations to UK 14304 (a selective alpha 2-adrenergic agonist), serotonin, and aggregating platelets were impaired 4 weeks after endothelium removal and remained so throughout the study. The endothelium-dependent relaxations to thrombin and adenosine diphosphate became depressed 8 weeks after endothelium removal and those to bradykinin became depressed 16 weeks after endothelium removal, while those to the calcium ionophore A23187 were maintained throughout the study. Endothelium-dependent relaxations to all vasoactive agents were unaltered in the control arteries. In the control arteries, pertussis toxin, an inhibitor of certain G proteins, markedly inhibited the endothelium-dependent relaxations to UK 14304 and serotonin and partially inhibited those to thrombin and aggregating platelets. The responses inhibited by the toxin in control arteries were significantly reduced in the reduced in the previously denuded arteries with regenerated endothelium. The inhibitory effect of pertussis toxin was markedly reduced in those arteries with regenerated endothelium. In quiescent rings, the presence of normal endothelium inhibited the contractions caused by serotonin and aggregating platelets; this endothelium-dependent depression was markedly impaired in the previously denuded arteries throughout the study. Direct relaxation of the coronary smooth muscle to nitric oxide or sodium nitroprusside or direct contraction to KCl or serotonin were comparable between the control and previously denuded arteries. These experiments indicate that endothelium-dependent relaxations progressively worsen after regeneration of the endothelium and that the dysfunction of a pertussis toxin-sensitive G protein partly account for the endothelial dysfunction in the chronic regenerated state.
Look, no hands! Spectral biomarkers from genetic association studies
Authors: Michael Inouye, Gad Abraham
Journal: Genome Medicine (2013)

Recent advances in our understanding of the genomics of the human metabolome have shed light on the pathways involved in metabolic and cardiovascular disease. Such studies crucially depend on the interpretation of complex molecular spectra. A recent study by Suhre and colleagues provides a way to identify potentially clinically relevant biomarkers without a priori information, such as reference spectra, thus aiding the discovery of additional spectral features and corresponding genomic loci associated with metabolism and disease.
Clonal Heterogeneity, Experimental Metastatic Ability, and p21 Expression in H-ras-Transformed NIH 3T3 Cells
Authors: S. A. Hill, S. Wilson, A. F. Chambers
Journal: JNCI Journal of the National Cancer Institute (1988)

We examined individual clones of murine NIH 3T3 -cells, transformed with the human bladder cancer (T24) H-ras oncogene, for p21 expression and for experimental metastatic ability in the immunodeficient chick embryo. We found that the clones were heterogeneous for both of these properties. In general, p21 expression was a good predictor of metastatic ability of the clones. Cells from poorly metastatic clones were passaged in the chick embryo metastasis assay to determine whether cells with increased metastatic ability could be selected. We found that the selected cells were more metastatic and that substantial increases in expression of p21 also accompanied this increase in metastatic ability. The relationship between p21 expression and metastatic ability appeared linear, with a high correlation coefficient (r = .85), suggesting that in this model system quantitative increases in metastatic properties can result from increased expression of the ras oncogene protein product p21.
Cardiac Troponin T Predicts Mortality in Patients With End-Stage Renal Disease
Authors: Jutta Dierkes, Ute Domröse, Sabine Westphal, Andreas Ambrosch, Hans-Peter Bosselmann, Klaus Hinrich Neumann, Claus Luley
Journal: Circulation (2000)

Background —Patients with end-stage renal disease have a high risk of premature death, mainly as the result of cardiovascular disease (CVD), which is not sufficiently explained by the conventional risk factors. We therefore prospectively investigated total mortality and cardiovascular events in 102 patients on hemodialysis and assessed the prognostic value of baseline disease status and laboratory variables including total homocysteine and cardiac troponin T. Methods and Results —Patients were followed for 2 years or until their first event of CVD (for outcome variable cardiovascular events, n=33) or death (for outcome variable total mortality, n=28). Survival was computed by the Kaplan-Meier method. Cox proportional hazards model was used to determine independent predictors of CVD events or total mortality. Cardiac troponin T emerged as the most powerful predictor of mortality, resulting in an almost 7-fold risk increase at concentrations &gt;0.10 ng/mL (hazard ratio 6.85, 95% CI 3.04 to 15.45). Total homocysteine level greater than median was also associated with mortality (hazard ratio 2.44, 95% CI 1.10 to 5.40). These hazard ratios did not change substantially after adjustment for other risk factors. Significant predictors for CVD events were baseline diabetes, cerebrovascular disease, serum glucose, and triglycerides. After adjustment, only glucose and triglycerides remained significantly related to CVD events (hazard ratio with 95% CI 1.33 [1.12 to 1.57] and 1.14 [1.04 to 1.26], respectively, for a 1-mmol/L increase in concentration). Conclusions —We conclude that total homocysteine and particularly cardiac troponin T are important predictors of mortality in patients with end-stage renal disease, whereas other laboratory variables and baseline disease status have less prognostic value.
Rat Intestine Secretes Discoid High Density Lipoprotein
Authors: P. H. R. Green, A. R. Tall, R. M. Glickman
Journal: Journal of Clinical Investigation (1978)

High density lipoprotein was isolated from pooled rat serum and mesenteric lymph of lymph fistula rats. In most experiments, 5,5′-dithionitrobenzoic acid, an inhibitor of the enzyme lecithin:cholesterol acyltransferase, was added during the collection of lymph to prevent modification of the lipid composition of newly secreted lipoproteins. Negative staining electron microscopy of lymph high density lipoprotein revealed discoidal particles (190±3 × 55±1 Å) which tended to form rouleaux, smaller spherical particles were also present. Serum high density lipoprotein contained only spherical particles (diameter 93±4 Å). Lipid analysis showed that lymph high density lipoprotein was enriched in phospholipid and deficient in cholesterol esters when compared to serum high density lipoprotein. The phospholipid to cholesterol esters ratio was greatest in basal lymph high density lipoprotein when compared to fatty lymph and serum high density lipoprotein. From analysis of the lipid compositional data and direct particle measurement by electron microscopy, it could be determined that ≅50% of basal lymph high density lipoprotein and 30% of fatty lymph high density lipoprotein was discoid. Basal lymph high density lipoprotein was enriched in apoA-I and deficient in the arginine-rich peptide, and the apoprotein composition of fatty lymph high density lipoprotein more closely resembled serum. These observations demonstrate that intestinal lymph contains two types of high density lipoprotein particles, a discoid nascent particle deficient in cholesterol ester and rich in apoA-I, and spherical high density lipoprotein derived from plasma. A significant amount of lymph high density lipoprotein appears to be secreted by the intestine.
Interplay between Two Hormone-Independent Activation Domains in the Androgen Receptor
Authors: Leen Callewaert, Nora Van Tilborgh, Frank Claessens
Journal: Cancer Research (2006)

Abstract The androgen receptor (AR) plays a key role in prostate cancer development, as well as its treatments, even for the hormone-refractory state. Here, we report that an earlier described lysine-to-arginine mutation at position 179 in AR leads to a more potent AR. We show that two activation domains (Tau-1 and Tau-5) are necessary and sufficient for the full activity of AR and the intrinsic activity of the AR-NTD. Two α-helices surrounding the Lys179 define the core of Tau-1, which can act as an autonomous activation function, independent of p160 coactivators. Furthermore, we show that although the recruitment of p160 coactivators is mediated through Tau-5, this event is attenuated by core Tau-1. This better definition of the mechanisms of action of both Tau-1 and Tau-5 is instrumental for the design of alternative therapeutic strategies against prostate cancer. (Cancer Res 2006; 66(1): 543-53)