tbuckley/cabot-search huggingface dataset:
Relationship between Composition and Toxicity of Motor Vehicle Emission Samples
Authors: Jacob D. McDonald, Ingvar Eide, JeanClare Seagrave, Barbara Zielinska, Kevin Whitney, Douglas R. Lawson, Joe L. Mauderly
Journal: Environmental Health Perspectives (2004)

In this study we investigated the statistical relationship between particle and semivolatile organic chemical constituents in gasoline and diesel vehicle exhaust samples, and toxicity as measured by inflammation and tissue damage in rat lungs and mutagenicity in bacteria. Exhaust samples were collected from "normal" and "high-emitting" gasoline and diesel light-duty vehicles. We employed a combination of principal component analysis (PCA) and partial least-squares regression (PLS; also known as projection to latent structures) to evaluate the relationships between chemical composition of vehicle exhaust and toxicity. The PLS analysis revealed the chemical constituents covarying most strongly with toxicity and produced models predicting the relative toxicity of the samples with good accuracy. The specific nitro-polycyclic aromatic hydrocarbons important for mutagenicity were the same chemicals that have been implicated by decades of bioassay-directed fractionation. These chemicals were not related to lung toxicity, which was associated with organic carbon and select organic compounds that are present in lubricating oil. The results demonstrate the utility of the PCA/PLS approach for evaluating composition-response relationships in complex mixture exposures and also provide a starting point for confirming causality and determining the mechanisms of the lung effects.
The Liver: Biology and Pathobiology. Ed. 2. Edited by I. M. Arias, W. B. Jakoby, H. Popper, D. Schachter and D. S. Shafritz, 1,336 pp. New York: Raven Press, 1988 $105 00
Authors: Robert L. Carithers
Journal: Hepatology (1989)
A Phase I/II Study of Arsenic Trioxide/Bortezomib/Ascorbic Acid Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma
Authors: James R. Berenson, Jeffrey Matous, Regina A. Swift, Russell Mapes, Blake Morrison, Howard S. Yeh
Journal: Clinical Cancer Research (2007)

Abstract Purpose: This multicenter, open-label, phase I/II dose escalation study assessed the safety/tolerability and initial efficacy of arsenic trioxide/bortezomib/ascorbic acid (ABC) combination therapy in patients with relapsed/refractory multiple myeloma. Experimental Design: Enrolled in six cohorts, patients were given arsenic trioxide (0.125 or 0.250 mg/kg), bortezomib (0.7, 1.0, or 1.3 mg/m2), and a fixed dose of ascorbic acid (1 g) i.v. on days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles. The primary end point was safety/tolerability of the ABC regimen. Results: Twenty-two patients (median age, 63 years) were enrolled, having failed a median of 4 (range, 3-9) prior therapies. One occurrence of grade 4 thrombocytopenia was observed. One patient had asymptomatic arrhythmia and withdrew from the study. Objective responses were observed in 6 (27%) patients, including two partial responses and four minor responses. Median progression-free survival was 5 months (95% confidence interval, 2-9 months), and median overall survival had not been reached. The 12-month progression-free survival and overall survival rates were 34% and 74%, respectively. One (minor response) of six patients receiving the lowest dose of bortezomib (0.7 mg/m2) and 5 (2 partial responses and 3 minor responses) of 16 patients receiving the higher doses (1.0 or 1.3 mg/m2) responded. Conclusions: The ABC regimen was well tolerated by most patients, and it produced preliminary signs of efficacy with an objective response rate of 27% in this heavily pretreated study population. These findings warrant further clinical evaluation of the ABC combination for treatment of relapsed/refractory multiple myeloma.
Aerobic exercise effects on cognitive and neural plasticity in older adults
Authors: K I Erickson, A F Kramer
Journal: British Journal of Sports Medicine (2008)

<h3>Abstract</h3> Successful execution of goal-directed behaviors often requires the deployment of cognitive control, which is thought to require cognitive effort. Recent theories have proposed that anterior cingulate cortex (ACC) regulates control levels by weighing the reward-related benefits of control against its effort-related costs. However, given that the sensations of cognitive effort and reward valuation are available only to introspection, this hypothesis is difficult to investigate empirically. We have proposed that two electrophysiological indices of ACC function, frontal midline theta and the reward positivity (RewP), provide objective measures of these functions. To investigate this issue, we recorded the electroencephalogram (EEG) from participants engaged in an extended, cognitively-demanding task. Participants performed a time estimation task for 2 hours in which they received reward and error feedback according to their task performance. We observed that the amplitude of the RewP, a feedback-locked component of the event related brain potential associated with reward processing, decreased with time-on-task. Conversely, frontal midline theta power, which consists of 4-8 Hz EEG oscillations associated with cognitive effort, increased with time-on-task. We also examined how these phenomena changed over time by conducting within-participant multi-level modeling analyses. Our results suggest that extended execution of a cognitively-demanding task is characterized by an early phase in which high control levels combine with strong reward valuation to foster rapid improvements in task performance, and a later phase in which high control levels counteract waning reward valuation to maintain stable task performance.
Electropotential measurements as a new diagnostic modality for breast cancer
Authors: Jack Cuzick, Roland Holland, Volker Barth, Richard Davies, Mark Faupel, Ian Fentiman, HJ Frischbier, JL LaMarque, Mirella Merson, Virgilio Sacchini, Daniel Vanel, Umberto Veronesi
Journal: The Lancet (1998)
Elevated Plasma Factor VIII and D-Dimer Levels as Predictors of Poor Outcomes of Thrombosis in Children
Authors: Neil A Goldenberg, R Knapp-Clevenger, Marilyn J Manco-Johnson
Journal: New England Journal of Medicine (2004)

Elevated levels of plasma factor VIII and D-dimer predict recurrent venous thromboembolism in adults. We sought to determine whether an elevation of factor VIII, D-dimer, or both at diagnosis and persistence of the laboratory abnormality after three to six months of anticoagulant therapy correlate with poor outcomes of thrombosis in children.
Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche
Authors: Andrew Chow, Daniel Lucas, Andrés Hidalgo, Simón Méndez-Ferrer, Daigo Hashimoto, Christoph Scheiermann, Michela Battista, Marylene Leboeuf, Colette Prophete, Nico van Rooijen, Masato Tanaka, Miriam Merad, Paul S. Frenette
Journal: The Journal of Experimental Medicine (2011)

Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1hi monocytes (MOs), Gr-1lo MOs, and macrophages (MΦ) based on differential expression of Gr-1, CD115, F4/80, and CD169. Using MO and MΦ conditional depletion models, we found that reductions in BM mononuclear phagocytes led to reduced BM CXCL12 levels, the selective down-regulation of HSC retention genes in Nestin+ niche cells, and egress of HSCs/progenitors to the bloodstream. Furthermore, specific depletion of CD169+ MΦ, which spares BM MOs, was sufficient to induce HSC/progenitor egress. MΦ depletion also enhanced mobilization induced by a CXCR4 antagonist or granulocyte colony-stimulating factor. These results highlight two antagonistic, tightly balanced pathways that regulate maintenance of HSCs/progenitors in the niche during homeostasis, in which MΦ cross talk with the Nestin+ niche cell promotes retention, and in contrast, SNS signals enhance egress. Thus, strategies that target BM MΦ hold the potential to augment stem cell yields in patients that mobilize HSCs/progenitors poorly.
Phase I Studies of Interleukin (IL)-2 and Rituximab in B-Cell Non-Hodgkin’s Lymphoma
Authors: William Larry Gluck, Deborah Hurst, Alan Yuen, Alexandra M. Levine, Mark A. Dayton, Jon P. Gockerman, Jennifer Lucas, Kimberly Denis-Mize, Barbara Tong, Dawn Navis, Anita Difrancesco, Sandra Milan, Susan E. Wilson, Maurice Wolin
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Expansion and activation of natural killer (NK) cells with interleukin-2 (IL-2) may enhance antibody-dependent cellular cytotoxicity (ADCC), an important mechanism of rituximab activity. Two parallel Phase I studies evaluated combination therapy with rituximab and IL-2 in relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL). Experimental Design: Thirty-four patients with advanced NHL received rituximab (375 mg/m2 i.v. weekly, weeks 1–4) and escalating doses of s.c. IL-2 [2–7.5 MIU daily (n = 19) or 4.5–14 million international units three times weekly (n = 15), weeks 2–5]. Safety, tolerability, clinical responses, NK cell counts, and ADCC activity were evaluated. Results: Maximally tolerated doses (MTD) of IL-2 were 6 MIU daily and 14 million international units thrice weekly. The most common adverse events were fever, chills, and injection site reactions. Dose-limiting toxicities were fatigue and reversible liver enzyme test elevations. Of the 9 patients enrolled at the daily schedule MTD, 5 showed clinical response. On the thrice-weekly schedule at the MTD, 4 of 5 patients responded. Responders showed median time to progression of 14.9 and 16.1 months, respectively, for the two studies. For the same total weekly dose, thrice-weekly IL-2 administration induced greater increases in NK cell counts than daily dosing, and NK cells correlated with clinical response on the thrice-weekly regimen. ADCC activity was increased and maintained after IL-2 therapy in responding and stable disease patients. Conclusions: Addition of IL-2 to rituximab therapy is safe and, using thrice-weekly IL-2 dosing, results in NK cell expansion that correlates with response. This combination treatment regimen merits additional evaluation in a randomized clinical trial.
Microwaves from GSM Mobile Telephones Affect 53BP1 and γ-H2AX Foci in Human Lymphocytes from Hypersensitive and Healthy Persons
Authors: Eva Markovà, Lena Hillert, Lars Malmgren, Bertil R. R. Persson, Igor Y. Belyaev
Journal: Environmental Health Perspectives (2005)

The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (gamma-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/gamma-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects.
The Role of Amphiregulin in Exemestane-Resistant Breast Cancer Cells: Evidence of an Autocrine Loop
Authors: Xin Wang, Selma Masri, Sheryl Phung, Shiuan Chen
Journal: Cancer Research (2008)

Abstract Exemestane-resistant breast cancer cell lines (i.e., ExeR), derived from MCF-7 cells expressing a high level of aromatase (MCF-7aro), were generated in our laboratory. The epidermal growth factor (EGF)–like protein amphiregulin (AREG) was highly expressed in ExeR cells based on cDNA microarray analysis. The high levels of AREG mRNA in ExeR cell lines were confirmed by real-time reverse transcription-PCR. The high levels of AREG protein in ExeR cell lysates and culture media were confirmed by Western blot analysis and ELISA, respectively. Furthermore, our Western blot analysis showed that whereas no AREG was detected in the DMSO control, overnight treatment of parental MCF-7aro cells with 1 μmol/L exemestane strongly induced the expression of AREG. This induction was totally blocked by 100 nmol/L of pure antiestrogen ICI 182,780, implying estrogen receptor (ER) dependence of exemestane-induced AREG expression. MCF-7aro cells were not able to proliferate in hormone-free medium, but were able to proliferate in conditioned medium from ExeR cells, similar to the treatment of recombinant human AREG. Small interference RNA targeting AREG inhibited ExeR proliferation, confirming that AREG is truly functioning as a growth factor of ExeR cells. The specific inhibitors to ER (ICI 182,780), EGF receptor (EGFR; AG1478), and mitogen-activated protein kinase (MAPK; U0126) all showed dose-dependent suppression of the proliferation of ExeR cells, indicating the involvement of the ER, EGFR, and MAPK pathways. Based on these findings, we propose a possible mechanism that underlies exemestane resistance: exemestane induces AREG in an ER-dependent manner. AREG then activates the EGFR pathway and leads to the activation of the MAPK pathway that drives cell proliferation. [Cancer Res 2008;68(7):2259–65]
Maternal Plasma DNA Sequencing Reveals the Genome-Wide Genetic and Mutational Profile of the Fetus
Authors: Y. M. Dennis Lo, K. C. Allen Chan, Hao Sun, Eric Z. Chen, Peiyong Jiang, Fiona M. F. Lun, Yama W. Zheng, Tak Y. Leung, Tze K. Lau, Charles R. Cantor, Rossa W. K. Chiu
Journal: Science Translational Medicine (2010)

Sequencing plasma DNA from a pregnant woman permits genome-wide scanning for the mutational status of the fetus prenatally and noninvasively.
Postweaning Exposure to Aflatoxin Results in Impaired Child Growth: A Longitudinal Study in Benin, West Africa
Authors: Yunyun Gong, Assomption Hounsa, Sharif Egal, Paul C. Turner, Anne E. Sutcliffe, Andrew J. Hall, Kitty Cardwell, Christopher P. Wild
Journal: Environmental Health Perspectives (2004)

Aflatoxins are dietary contaminants that are hepatocarcinogenic and immunotoxic and cause growth retardation in animals, but there is little evidence concerning the latter two parameters in exposed human populations. Aflatoxin exposure of West African children is known to be high, so we conducted a longitudinal study over an 8-month period in Benin to assess the effects of exposure on growth. Two hundred children 16-37 months of age were recruited from four villages, two with high and two with low aflatoxin exposure (50 children per village). Serum aflatoxin-albumin (AF-alb) adducts, anthropometric parameters, information on food consumption, and various demographic data were measured at recruitment (February) and at two subsequent time points (June and October). Plasma levels of vitamin A and zinc were also measured. AF-alb adducts increased markedly between February and October in three of the four villages, with the largest increases in the villages with higher exposures. Children who were fully weaned at recruitment had higher AF-alb than did those still partially breast-fed (p < 0.0001); the major weaning food was a maize-based porridge. There was no association between AF-alb and micronutrient levels, suggesting that aflatoxin exposure was not accompanied by a general nutritional deficiency. There was, however, a strong negative correlation (p < 0.0001) between AF-alb and height increase over the 8-month follow-up after adjustment for age, sex, height at recruitment, socioeconomic status, village, and weaning status; the highest quartile of AF-alb was associated with a mean 1.7 cm reduction in growth over 8 months compared with the lowest quartile. This study emphasizes the association between aflatoxin and stunting, although the underlying mechanisms remain unclear. Aflatoxin exposure during the weaning period may be critical in terms of adverse health effects in West African children, and intervention measures to reduce exposure merit investigation.
Influence of Glucose on the Transmembrane Action Potential of Guinea-Pig Papillary Muscle
Authors: K. PRASAD, DON P. MACLEOD
Journal: Circulation Research (1969)

In a previous report, we have proposed that anaerobic glycolysis alone can maintain an action potential of normal duration in guinea-pig papillary muscle. This proposal followed from the observation that 50 mM glucose, several sympathomimetic amines, and aminophylline all caused the duration of the action potential of muscles, which had been reduced by incubation in a medium containing 5 mM glucose, to return toward control values. This occurred in the presence or absence of oxygen. It was further proposed that the ATP resulting from anaerobic glycolysis was in some way preferentially utilized in the membrane by a process controlling repolarization and therefore the duration of the action potential. The present experiments were undertaken to determine what metabolic pathways were necessary for the glucose effect mentioned above, by the use of the metabolic inhibitors sodium cyanide, iodoacetic acid, and 2,4-dinitrophenol. Secondly, the effects of ouabain and calcium, which are known to modulate the utilization of ATP, on the glucose effect were studied. It was concluded that an intact glycolytic pathway is necessary for the effect of glucose on the electrical activity of papillary muscle and that the effect can be increased or decreased by low or high doses of ouabain, respectively. The actions of ouabain are thought to be due to a stimulation and depression of a membrane ATP-ase.
Electroneutral K+/HCO3- cotransport in cells of medullary thick ascending limb of rat kidney.
Authors: F Leviel, P Borensztein, P Houillier, M Paillard, M Bichara
Journal: Journal of Clinical Investigation (1992)

The renal medullary thick ascending limb (MTAL) of the rat absorbs bicarbonate through luminal H+ secretion and basolateral HCO3- transport into the peritubular space. To characterize HCO3- transport, intracellular pH (pHi) was monitored by use of the pH-sensitive fluorescent probe (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein in fresh suspensions of rat MTAL tubules. When cells were preincubated in HCO3-/CO2-containing solutions and then abruptly diluted into HCO3-/CO2-free media, the pHi response was an initial alkalinization due to CO2 efflux, followed by an acidification (pHi recovery). The pHi recovery required intracellular HCO3-, was inhibited by 10(-4) M diisothiocyanostilbene-2-2'-disulphonic acid (DIDS), and was not dependent on Cl- or Na+. As assessed by use of the cell membrane potential-sensitive fluorescent probe 3,3'-dipropylthiadicarbocyanine, cell depolarization by abrupt Cl- removal from or addition of 2 mM barium into the external medium did not affect HCO3(-)-dependent pHi recovery, and the latter was not associated per se with any change in potential difference, which indicated that HCO3- transport was electroneutral. The HCO3(-)-dependent pHi recovery was inhibited by raising extracellular potassium concentration and by intracellular potassium depletion. Finally, as measured by use of a K(+)-selective extracellular electrode, a component of K+ efflux out of the cells was HCO3- dependent and DIDS sensitive. The results provide evidence for an electroneutral K+/HCO3- cotransport in rat MTAL cells.
Endocrine and Paracrine Regulation of Birth at Term and Preterm*
Authors: John R.G. Challis, Stephen G. Matthews, William Gibb, Stephen J. Lye
Journal: Endocrine Reviews (2000)

Abstract We have examined factors concerned with the maintenance of uterine quiescence during pregnancy and the onset of uterine activity at term in an animal model, the sheep, and in primate species. We suggest that in both species the fetus exerts a critical role in the processes leading to birth, and that activation of the fetal hypothalamic-pituitary-adrenal axis is a central mechanism by which the fetal influence on gestation length is exerted. Increased cortisol output from the fetal adrenal gland is a common characteristic across animal species. In primates, there is, in addition, increased output of estrogen precursor from the adrenal in late gestation. The end result, however, in primates and in sheep is similar: an increase in estrogen production from the placenta and intrauterine tissues. We have revised the pathway by which endocrine events associated with parturition in the sheep come about and suggest that fetal cortisol directly affects placental PGHS expression. In human pregnancy we suggest that cortisol increases PGHS expression, activity, and PG output in human fetal membranes in a similar manner. Simultaneously, cortisol contributes to decreases in PG metabolism and to a feed-forward loop involving elevation of CRH production from intrauterine tissues. In human pregnancy, there is no systemic withdrawal of progesterone in late gestation. We have argued that high circulating progesterone concentrations are required to effect regionalization of uterine activity, with predominantly relaxation in the lower uterine segment, allowing contractions in the fundal region to precipitate delivery. This new information, arising from basic and clinical studies, should further the development of new methods of diagnosing the patient at risk of preterm labor, and the use of scientifically based strategies specifically for the management of this condition, which will improve the health of the newborn.
Free internal mammary artery for coronary bypass.
Authors: B A Vidne, A B Lee, T Z Lajos, G Schimert
Journal: Thorax (1976)

An improved technique of free internal mammary artery (IMA) to ascending aorta anastomosis for coronary bypass is described. A small patch vein with a suitable side branch or branches is interposed, connecting the proximal end of a detached IMA to the ascending aorta. A single or double free IMA alone or in combination with an additional saphenous vein graft was performed in 77 patients. A total of 125 free IMA grafts were done. The hospital mortality was 2-7% and late mortality 1-4%. Seventy-one of the 74 surviving patients had no angina and returned to a normal life. Postoperative coronary arteriography in 65 patients showed a patency rate of 96%. On year's experience with this technique is very encouraging. However, prolonged follow-up is necessary to determine if free IMA, as used by us, will increase the long-term patency rate.