tbuckley/cabot-search huggingface dataset:
Hepatic energy state is regulated by glucagon receptor signaling in mice
Authors: Eric D. Berglund, Robert S. Lee-Young, Daniel G. Lustig, Sara E. Lynes, E. Patrick Donahue, Raul C. Camacho, M. Elizabeth Meredith, Mark A. Magnuson, Maureen J. Charron, David H. Wasserman
Journal: Journal of Clinical Investigation (2009)

The hepatic energy state, defined by adenine nucleotide levels, couples metabolic pathways with energy requirements. This coupling is fundamental in the adaptive response to many conditions and is impaired in metabolic disease. We have found that the hepatic energy state is substantially reduced following exercise, fasting, and exposure to other metabolic stressors in C57BL/6 mice. Glucagon receptor signaling was hypothesized to mediate this reduction because increased plasma levels of glucagon are characteristic of metabolic stress and because this hormone stimulates energy consumption linked to increased gluconeogenic flux through cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) and associated pathways. We developed what we believe to be a novel hyperglucagonemic-euglycemic clamp to isolate an increment in glucagon levels while maintaining fasting glucose and insulin. Metabolic stress and a physiological rise in glucagon lowered the hepatic energy state and amplified AMP-activated protein kinase signaling in control mice, but these changes were abolished in glucagon receptor- null mice and mice with liver-specific PEPCK-C deletion. 129X1/Sv mice, which do not mount a glucagon response to hypoglycemia, displayed an increased hepatic energy state compared with C57BL/6 mice in which glucagon was elevated. Taken together, these data demonstrate in vivo that the hepatic energy state is sensitive to glucagon receptor activation and requires PEPCK-C, thus providing new insights into liver metabolism.
Promoter methylation of Bcl-2 in CSE-induce HUVEC apoptosis
Authors: Huihui Zeng, Ping Chen
Journal: European Respiratory Journal (2013)

Endothelia apoptosis participates copd and other diseases induced by smoking. We discussed whether Bcl-2 participated in cigarette smoke extract (CSE)-induce HUVEC apoptosis. Given the methylation in promoter causing gene silencing and existence of CpG islands in Bcl-2 promoter, we hypothesized that Bcl-2 methylation might induce the apoptosis.  Method: HUVEC was treated with different CSE concentration. We divided and treated cells into four groups: control, 5%CSE, 5%CSE+AZA (demethylation reagent), and AZA. The apoptotic index, expression and methylation status of Bcl-2 were assessed through flowcytometry, westernblotting, and BSP respectively.  Result: 1.CSE decreased Bcl-2 depend on concentation (Figure 1), and AZA prevented this abnormality.  2.CSE increased methylation of Bcl-2 promoter (14.55±3.15) %, though AZA prevented the deregulation[(1.82±1.57) % P  3.The regression analysis showed a relationship between Bcl-2 expression,apoptosis and methylation.  Conclusion: CSE induced abnormal methylation of Bcl-2 promoter, which might participate endothelia apoptosis. This high methylation of Bcl-2 promoter might be involved in COPD and other endothelia relative diseases.
Increase of lipid fluidity and suppression of proliferation resulting from liposome uptake by human keratinocytes in vitro
Authors: B. BONNEKOH, J. RODING, G. R. F. KRUEGER, M. GHYCZY, G. MAHRLE
Journal: British Journal of Dermatology (1991)

The in vitro effects of liposomes on HaCaT human keratinocytes were studied with regard to their uptake, lipid fluidity and proliferation of the cells. Oligolamellar liposomes, prepared from soya bean phospholipids, had a mean size of 150 mm and consisted predominantly of phosphatidylcholine (83%) and phosphatidylethanolamine (10%) and the fatty acids comprised mainly linoleic acid (66%) or other unsaturated fatty acids. After 6 and 24 h of incubation with 1 and 0.1% w/v of liposomal lipids, phase-contrast microscopy revealed marked cytoplasmic vacuolization of the cells. Keratinocytes treated with the liposomes contained aggregations of multilaminated lipid material without delimiting cell membranes. The cellular lipid fluidity (reciprocal of diphenylhexatriene fluorescence polarization P-value) correlated with liposomal concentration and incubation time. A significant elevation of lipid fluidity (P less than 0.05) was observed with 1 and 0.1% liposomes after 1 h of incubation (81.8 +/- 4.7 and 95.7 +/- 1.2% of control P value) and for 0.01% liposomes after 3 h (96.2 +/- 1.5%). Maximum fluidity occurred after 48 h of exposure to 1% liposomes (42.1 +/- 3.1%). Exposure to liposomal lipids for 24 and 48 h resulted in suppressed cell proliferation with 50% inhibition concentrations (IC50), being 0.06% for incorporation of [3H]-thymidine. 0.08% for [14C]-amino-acid incorporation and greater than 1% for protein content per well after 24 h of exposure. The cells were able to proliferate and lipid fluidity returned to normal within 7 days following discontinuation of incubation with liposomal lipids.
<i>MGMT</i>-STP27 Methylation Status as Predictive Marker for Response to PCV in Anaplastic Oligodendrogliomas and Oligoastrocytomas. A Report from EORTC Study 26951
Authors: Martin J. van den Bent, Lale Erdem-Eraslan, Ahmed Idbaih, Johan de Rooi, Paul H.C. Eilers, Wim G.M. Spliet, Wilfred F.A. den Dunnen, Cees Tijssen, Pieter Wesseling, Peter A.E. Sillevis Smitt, Johan M. Kros, Thierry Gorlia, Pim J. French
Journal: Clinical Cancer Research (2013)

The long-term follow-up results from the EORTC-26951 trial showed that the addition of procarbazine, CCNU, and vincristine (PCV) after radiotherapy increases survival in anaplastic oligodendrogliomas/oligoastrocytomas (AOD/AOA). However, some patients appeared to benefit more from PCV treatment than others.We conducted genome-wide methylation profiling of 115 samples included in the EORTC-26951 trial and extracted the CpG island hypermethylated phenotype (CIMP) and MGMT promoter methylation (MGMT-STP27) status.We first show that methylation profiling can be conducted on archival tissues with a performance that is similar to snap-frozen tissue samples. We then conducted methylation profiling on EORTC-26951 clinical trial samples. Univariate analysis indicated that CIMP+ or MGMT-STP27 methylated tumors had an improved survival compared with CIMP- and/or MGMT-STP27 unmethylated tumors [median overall survival (OS), 1.05 vs. 6.46 years and 1.06 vs. 3.8 years, both P < 0.0001 for CIMP and MGMT-STP27 status, respectively]. Multivariable analysis indicates that CIMP and MGMT-STP27 are significant prognostic factors for survival in presence of age, sex, performance score, and review diagnosis in the model. CIMP+ and MGMT-STP27 methylated tumors showed a clear benefit from adjuvant PCV chemotherapy: the median OS of CIMP+ samples in the RT and RT-PCV arms was 3.27 and 9.51 years, respectively (P = 0.0033); for MGMT-STP27 methylated samples, it was 1.98 and 8.65 years. There was no such benefit for CIMP- or for MGMT-STP27 unmethylated tumors. MGMT-STP27 status remained significant in an interaction test (P = 0.003). Statistical analysis of microarray (SAM) identified 259 novel CpGs associated with treatment response.MGMT-STP27 may be used to guide treatment decisions in this tumor type.
Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7Rα mutant mice
Authors: Lisa C. Osborne, Salim Dhanji, Jonathan W. Snow, John J. Priatel, Melissa C. Ma, M. Jill Miners, Hung-Sia Teh, Mark A. Goldsmith, Ninan Abraham
Journal: The Journal of Experimental Medicine (2007)

Loss of interleukin (IL)-7 or the IL-7 receptor alpha (IL-7Rα, CD127) results in severe immunodeficiencies in mice and humans. To more precisely identify signals governing IL-7 function in vivo, we have disrupted the IL-7Rα Y449XXM motif in mice by knock-in mutagenesis (IL-7Rα449F). Thymic precursors were reduced in number in IL-7Rα449F mice, but in marked contrast to IL-7Rα−/− knockout mice, thymocytes and peripheral T cells developed normally. Strikingly, Listeria infection revealed that CD4 and CD8 T cells had different requirements for IL-7Rα signals. CD4 T cells failed to mount a primary response, but despite normal CD8 primary responses, maintenance of CD8 memory was impaired in IL-7Rα449F mice. Furthermore, we show that Bcl-2 is IL-7Rα Y449 independent and insufficient for IL-7–mediated maintenance of CD8 memory.
Polymorphisms in Cytokine and Cellular Adhesion Molecule Genes and Susceptibility to Hematotoxicity among Workers Exposed to Benzene
Authors: Qing Lan, Luoping Zhang, Min Shen, Martyn T. Smith, Guilan Li, Roel Vermeulen, Stephen M. Rappaport, Matthew S. Forrest, Richard B. Hayes, Martha Linet, Mustafa Dosemeci, Blanche P. Alter, Rona S. Weinberg, Songnian Yin, Meredith Yeager, Robert Welch, Suramya Waidyanatha, Sungkyoon Kim, Stephen Chanock, Nathaniel Rothman
Journal: Cancer Research (2005)

Abstract Benzene is a recognized hematotoxin and leukemogen but its mechanism of action and the role of genetic susceptibility are still unclear. Cytokines, chemokines, and cellular adhesion molecules are soluble proteins that play an important regulatory role in hematopoiesis. We therefore hypothesized that variation in these genes could influence benzene-induced hematotoxicity. We analyzed common, well-studied single-nucleotide polymorphisms (SNPs) in 20 candidate genes drawn from these pathways in a study of 250 workers exposed to benzene and 140 unexposed controls in China. After accounting for multiple comparisons, SNPs in five genes were associated with a statistically significant decrease in total WBC counts among exposed workers [IL-1A (−889C&amp;gt;T), IL-4 (−1098T&amp;gt;G), IL-10 (−819T&amp;gt;C), IL-12A (8685G&amp;gt;A), and VCAM1 (−1591T&amp;gt;C)], and one SNP [CSF3 (Ex4−165C&amp;gt;T)] was associated with an increase in WBC counts. The adhesion molecule VCAM1 variant was particularly noteworthy as it was associated with a decrease in B cells, natural killer cells, CD4+ T cells, and monocytes. Further, VCAM1 (−1591T&amp;gt;C) and CSF3 (Ex4−165C&amp;gt;T) were associated, respectively, with decreased (P = 0.041) and increased (P = 0.076) CFU-GEMM progenitor cell colony formation in 29 benzene-exposed workers. This is the first report to provide evidence that SNPs in genes that regulate hematopoiesis influence benzene-induced hematotoxicity.
Determinants of fast marathon performance: low basal sympathetic drive, enhanced postcompetition vasodilatation and preserved cardiac performance after competition
Authors: G Gratze, H Mayer, F C Luft, F Skrabal
Journal: British Journal of Sports Medicine (2008)

To test the hypothesis that enhanced postexercise vasodilatation is related to sympathetic drive to resistance vessels and to fast marathon performance.Prospective field study before and after running a marathon.51 healthy amateur runners who volunteered to participate. The fastest competitor finished fourth, the slowest 1290 th out of 1324 participants.None.Competition time, beat-to-beat blood pressure by the vascular unloading technique, oscillometric blood pressure, beat-to-beat stroke volume by impedance cardiography, total peripheral resistance changes calculated from blood pressure and stroke volume changes, sympathetic modulation of vasomotor tone and parasympathetic modulation of sinus node function by spectral analysis of blood pressure and heart rate variability, baroreceptor reflex sensitivity by the sequence method.Slow performers, in contrast to fast performers, exhibited a higher 0.1 Hz band of diastolic blood pressure variability before the competition (0.1 Hz BPV) (40.0 (SD 2.39) vs 54.9 (2.47), p<0.001), diminished vasodilatation (-11.3 (4.78) vs -29.4 (3.23), p<0.01) and a decrease in stroke index (-14.9 (3.55) vs +0.9 (3.37), p<0.001) in response to the race. Single and multiple regression analyses further corroborated the findings.Fast performance in the marathon is associated with low sympathetic modulation of vasomotor tone, maintained stroke index postcompetition and enhanced exercise-induced vasodilatation. We postulate that maintaining a low level of sympathetic modulation to resistance vessels during the course of training may indicate its appropriateness, thus enabling fast performance by optimal postexercise vasodilatation and by prevention of postcompetition cardiac dysfunction. This will have to be tested in future longitudinal studies.
Shortening Infusion Time for High-Dose Methotrexate Alters Antileukemic Effects: A Randomized Prospective Clinical Trial
Authors: Torben S. Mikkelsen, Alex Sparreboom, Cheng Cheng, Yinmei Zhou, James M. Boyett, Susana C. Raimondi, John C. Panetta, W. Paul Bowman, John T. Sandlund, Ching-Hon Pui, Mary V. Relling, William E. Evans
Journal: Journal of Clinical Oncology (2011)

To determine whether shortening the infusion duration of high-dose methotrexate (HDMTX; 1 g/m(2)) affects the in vivo accumulation of active methotrexate polyglutamates (MTXPG(1-7)) in leukemia cells and whether this differs among major acute lymphoblastic leukemia (ALL) subtypes.From June 2000 through October 2007, 356 children with ALL were randomly assigned to receive initial single-agent treatment with HDMTX (1 g/m(2)) as either a 24-hour infusion or a 4-hour infusion at two pediatric hospitals in the United States. The primary outcome measures were the accumulation of MTXPG(1-7) in leukemia cells and the antileukemic effects (eg, inhibition of de novo purine synthesis in bone marrow ALL cells, and decrease in circulating ALL cells).The 24-hour infusion resulted in significantly higher amounts of MTXPG(1-7) in bone marrow leukemia cells (median: 1,695 v 1,150 pmol/10(9) cells, P = .0059), and better antileukemic effects. The 24-hour infusion had the greatest effect on MTXPG(1-7) accumulation in hyperdiploid ALL (median: 3,919 v 2,417 pmol/10(9) cells, P = .0038); T-cell ALL exhibited smaller differences in MTXPG(1-7) but greater antileukemic effects with the longer infusion (median decrease in leukemia cells: 88.4% v 51.8%, P = .0075). In contrast, infusion duration had no significant impact on MTXPG(1-7) accumulation or antileukemic effects in ALL with the t(12;21)/(ETV6-RUNX1) chromosomal translocation.Shortening the infusion time of HDMTX reduces accumulation of active methotrexate in leukemia cells and decreases antileukemic effects, with differing consequences among major ALL subtypes.
Local Temperature Regulation of Microtissue Clearance from Rat Skeletal Muscle
Authors: Chester Hyman, Rita L. Paldino
Journal: Circulation Research (1962)

The influence of local temperature changes on the effective blood flow in the rat spinotrapezius muscle was investigated by the extension of the microtissue clearance technique originally used for frog mesentery. The clearance of water blue from microinjection sites in rat skeletal muscle at 37 C. agrees favorab1y with the clearance of other crystalloid labels from gross injection sites in skeletal muscle of mammalian forms. The data show a direct relationship between clearance rates and temperature over a range of 25 to 45 C. The µ value for clearance agrees with the µ value computed from forearm muscle blood flow measurements, at corresponding temperature ranges.
The influence of bovine colostrum supplementation on exercise performance in highly trained cyclists
Authors: C M Shing, D G Jenkins, L Stevenson, J S Coombes
Journal: British Journal of Sports Medicine (2006)

Purpose: The aim of this experiment was to investigate the influence of low dose bovine colostrum supplementation on exercise performance in cyclists over a 10 week period that included 5 days of high intensity training (HIT). Methods: Over 7 days of preliminary testing, 29 highly trained male road cyclists completed a VO 2max test (in which their ventilatory threshold was estimated), a time to fatigue test at 110% of ventilatory threshold, and a 40 km time trial (TT 40 ). Cyclists were then assigned to either a supplement (n = 14, 10 g/day bovine colostrum protein concentrate (CPC)) or a placebo group (n = 15, 10 g/day whey protein) and resumed their normal training. Following 5 weeks of supplementation, the cyclists returned to the laboratory to complete a second series of performance testing (week 7). They then underwent five consecutive days of HIT (week 8) followed by a further series of performance tests (week 9). Results: The influence of bovine CPC on TT 40 performance during normal training was unclear (week 7: 1±3.1%, week 9: 0.1±2.1%; mean±90% confidence limits). However, at the end of the HIT period, bovine CPC supplementation, compared to the placebo, elicited a 1.9±2.2% improvement from baseline in TT 40 performance and a 2.3±6.0% increase in time trial intensity (% VO 2max ), and maintained TT 40 heart rate (2.5±3.7%). In addition, bovine CPC supplementation prevented a decrease in ventilatory threshold following the HIT period (4.6±4.6%). Conclusion: Low dose bovine CPC supplementation elicited improvements in TT 40 performance during an HIT period and maintained ventilatory threshold following five consecutive days of HIT.
Occupational asthma caused by ethanolamines
Authors: B. Savonius, H. Keskinen, M. Tuppurainen, L. Kanerva
Journal: Allergy (1994)

Amino alcohols are used in various industries, often as minor constituents of compounds to modify the properties of the compound. Generally, they are considered to be safe, but they have been known to cause local skin irritation at higher concentrations in solutions. We report on three cases of occupational asthma caused by ethanolamines: two metal workers exposed to a cutting fluid containing triethanolamine, and one cleaner exposed to a detergent containing monoethanolamine. The diagnosis was based on work‐related symptoms and on a chamber challenge with the suspected agent. Persistence of the symptoms after exposure ended was a common feature of the three cases.
Quality of Life in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib or Interferon Alfa: Results From a Phase III Randomized Trial
Authors: David Cella, Jim Z. Li, Joseph C. Cappelleri, Andrew Bushmakin, Claudie Charbonneau, Sindy T. Kim, Isan Chen, Robert J. Motzer
Journal: Journal of Clinical Oncology (2008)

In an international, randomized phase III trial, sunitinib demonstrated statistically significant efficacy over interferon alfa (IFN-alpha) as first-line therapy in patients with metastatic renal cell carcinoma (mRCC) (progression-free survival time, 11 v 5 months, respectively; P < .001; objective response rate, 31% v 6%, respectively; P < .001). We report health-related quality-of-life (QOL) results from this trial.Seven hundred fifty mRCC patients were randomly assigned to sunitinib (6-week cycles: 50 mg orally once daily for 4 weeks, followed by 2 weeks off) or IFN-alpha (9 million units subcutaneous injections, three times weekly). QOL measures included the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index-15 item (FKSI-15), and the EuroQoL-5D's utility score (EQ-5D Index) and its visual analog scale (EQ-VAS). The primary QOL end point was the FKSI Disease-Related Symptoms (FKSI-DRS) subscale. Higher scores indicated better outcomes (better QOL or fewer symptoms). Data were analyzed for the intent-to-treat population using mixed-effects models, supplemented with pattern-mixture models.Patients receiving sunitinib reported higher FKSI-15 and FKSI-DRS scores at each cycle than those receiving IFN-alpha, with a significant difference in the overall least squares means (3.27 and 1.98, respectively; P < .0001). Similarly, differences in least squares means for FACT-G (and all subscales), EQ-5D Index, and EQ-VAS were all significantly favorable for sunitinib (P < .01). Per pre-established thresholds, between-treatment differences in the mean scores were clinically meaningful after cycle 4 for FKSI-DRS and at all assessments for FKSI-15, FACT-G, and the FACT-G functional well-being subscale.Sunitinib provides superior QOL compared with IFN-alpha in mRCC patients.
A Cross-Cultural Survey of Symptoms in Depression
Authors: WILLIAM W. K. ZUNG
Journal: American Journal of Psychiatry (1969)

Using his Self-Rating Depression Scale in six foreign countries, the author found that self-ratings of depressed patients were comparable between countries and differed significantly from scores of normal subjects and nondepressed patients. There was high correlation between the self-ratings and physicians' global ratings of depressed patients, and between scores on this test and other specific depression rating scales.
ANTIGEN RETENTION IN THE RABBIT
Authors: Kingsley M. Stevens
Journal: The Journal of Experimental Medicine (1953)

Normal and irradiated rabbits were given small doses of I(131) bovine gamma globulin (BGG) and the rates of its loss from their blood were determined. The figures agreed with those of previous reports. 3 to 4 months later, both groups were reinjected with antigen. The control group gave an accelerated (anamnestic) rate of loss, indicative of the immune state. The irradiated group gave a response similar to that given by the control group on primary injection. Rabbits recover from 500 roentgens of x-ray in less than 2 months. Hence, rabbits given BGG soon after irradiation should become immune to this antigen in 2 months if they retain it. Since rabbits reinjected with BGG 3 to 4 months after irradiation did not give an accelerated response, the BGG must not have been retained over the period of time necessary for recovery; i.e., less than 2 months. As the rate of antigen loss is greater in normal than in irradiated animals, normal rabbits will have lost BGG as active antigen prior to the irradiated animals. The amounts of antigen used (0.25 to 0.4 mg./kg.) more nearly approximate the amounts present during disease than have the amounts used in previous studies of antigen retention. The hypothesis that protein antigens are lost as fast or faster than homologous proteins is discussed and the conclusion reached that this is a valid concept.
Population-level effect of HIV on adult mortality and early evidence of reversal after introduction of antiretroviral therapy in Malawi
Authors: Andreas Jahn, Sian Floyd, Amelia C Crampin, Frank Mwaungulu, Hazzie Mvula, Fipson Munthali, Nuala McGrath, Johnbosco Mwafilaso, Venance Mwinuka, Bernard Mangongo, Paul EM Fine, Basia Zaba, Judith R Glynn
Journal: The Lancet (2008)
Rapid haplotype inference for nuclear families
Authors: Amy L Williams, David E Housman, Martin C Rinard, David K Gifford
Journal: Genome biology (2010)

Hapi is a new dynamic programming algorithm that ignores uninformative states and state transitions in order to efficiently compute minimum-recombinant and maximum likelihood haplotypes. When applied to a dataset containing 103 families, Hapi performs 3.8 and 320 times faster than state-of-the-art algorithms. Because Hapi infers both minimum-recombinant and maximum likelihood haplotypes and applies to related individuals, the haplotypes it infers are highly accurate over extended genomic distances.