tbuckley/cabot-search huggingface dataset:
Incorporation, distribution, and turnover of arachidonic acid within membrane phospholipids of B220+ T cells from autoimmune-prone MRL-lpr/lpr mice.
Authors: M Tomita-Yamaguchi, J F Babich, R C Baker, T J Santoro
Journal: The Journal of Experimental Medicine (1990)

The metabolism of AA-containing phosphoglycerides within T cell membranes leads to the generation of second messengers that appear to play a crucial role in transmembrane signal transduction. To test the hypothesis that aberrations in the movement of arachidonoyl-phospholipids are associated with and may potentially contribute to abnormal T cell function, the incorporation, distribution, and turnover of AA within the membrane glycerolipids of cells that are known to exhibit immunoregulatory disturbances was examined. Thy-1+, Ly-1+, L3T4-, Lyt-2-, B220+ T cells from autoimmune MRL-lpr/lpr mice were used as the cellular model. In contrast to control lymph node T cells, which preferentially incorporate labeled AA into phosphatidylcholine (PC), B220+ T cells displayed a predilection for distributing [3H]arachidonate into phosphatidylinositol (PI). The arachidonoyl-phospholipid pools were normal in B220+ T cells. The constitutive turnover of [3H]arachidonoyl-PI was significantly enhanced and that of [3H]arachidonate-PC substantially reduced in B220+ T cell compared with control cells. Using membrane homogenates B220+ T cells demonstrated a functional increase in the levels of lyso-PI. Intact B220+ T cells prelabeled with [3H]myoinositol and cultured in the absence of stimulation with exogenous antigens or mitogens, exhibited increased production of lyso-PI. The data indicate that the preferential formation of [3H]arachidonoyl-PI in B220+ T cells is the result of greatly increased, constitutive PI turnover that appears to be due to a membrane phospholipase A2 activity. It remains possible that disturbances in the movement of arachidonate within phospholipids of B220+ T cells play a role in the expression of aberrant immunological activity.
THE EFFECTS OF BACTERIAL ENDOTOXIN ON LIPIDE METABOLISM
Authors: V. S. LeQuire, J. D. Hutcherson, R. L. Hamilton, M. E. Gray
Journal: The Journal of Experimental Medicine (1959)

Single intravenous injections of Shear's polysaccharide in varying dosages invariably produced an elevation in the levels of the total serum lipides 24 hours after injection of endotoxin. The total serum cholesterol and lipide phosphorus were also affected, although they did not change with smaller doses of endotoxin and were rarely elevated to the same degree as were the total serum lipides. The degree of elevation of the serum lipides was apparently related to the amount of endotoxin injected up to a certain point, beyond which there was no further increase. There were two types of response to endotoxin by the serum lipides, a moderate increase and an uncontrolled increase. Higher dosages of endotoxin and fasting apparently increased the incidence of the latter response. No direct correlation could be made between serum lipide responses and histologic evidence typical of the generalized Shwartzman reaction following this regimen of endotoxin injection. The Shwartzman reaction did occur with greater frequency and with lower dosages of endotoxin in fasted animals. Animals given repeated injections of endotoxin showed an initial increase in serum lipides followed by a progressive decrease to normal levels as tolerance to the febrile action of endotoxin appeared. The febrile tolerance as well as the unresponsiveness of the serum lipides to endotoxin was abolished by thorium dioxide (thorotrast) in these animals. In similar experiments a "breakthrough" of lipide unresponsiveness to endotoxin was obtained by increasing the amount of endotoxin injected. Some of the implications of these results for the metabolic alterations produced by bacterial endotoxins are discussed.
LRH-1–dependent glucose sensing determines intermediary metabolism in liver
Authors: Maaike H. Oosterveer, Chikage Mataki, Hiroyasu Yamamoto, Taoufiq Harach, Norman Moullan, Theo H. van Dijk, Eduard Ayuso, Fatima Bosch, Catherine Postic, Albert K. Groen, Johan Auwerx, Kristina Schoonjans
Journal: Journal of Clinical Investigation (2012)

Liver receptor homolog 1 (LRH-1), an established regulator of cholesterol and bile acid homeostasis, has recently emerged as a potential drug target for liver disease. Although LRH-1 activation may protect the liver against diet-induced steatosis and insulin resistance, little is known about how LRH-1 controls hepatic glucose and fatty acid metabolism under physiological conditions. We therefore assessed the role of LRH-1 in hepatic intermediary metabolism. In mice with conditional deletion of Lrh1 in liver, analysis of hepatic glucose fluxes revealed reduced glucokinase (GCK) and glycogen synthase fluxes as compared with those of wild-type littermates. These changes were attributed to direct transcriptional regulation of Gck by LRH-1. Impaired glucokinase-mediated glucose phosphorylation in LRH-1–deficient livers was also associated with reduced glycogen synthesis, glycolysis, and de novo lipogenesis in response to acute and prolonged glucose exposure. Accordingly, hepatic carbohydrate response element-binding protein activity was reduced in these animals. Cumulatively, these data identify LRH-1 as a key regulatory component of the hepatic glucose-sensing system required for proper integration of postprandial glucose and lipid metabolism.
AIEC pathobiont instigates chronic colitis in susceptible hosts by altering microbiota composition
Authors: Benoit Chassaing, Omry Koren, Frederic A Carvalho, Ruth E Ley, Andrew T Gewirtz
Journal: Gut (2013)

<h3>Background</h3> Inflammatory bowel disease (IBD) is driven by a seemingly aberrant immune response to the gut microbiota with disease development dictated by genetics and environmental factors. A model exemplifying this notion is our recent demonstration that colonisation of adherent-invasive <i>Escherichia coli</i> (AIEC) during microbiota acquisition drove chronic colitis in mice lacking the flagellin receptor TLR5 (T5KO). T5KO colitis persisted beyond AIEC clearance and requires TLR4 and the NLRC4 inflammasome. We hypothesised that AIEC instigates chronic inflammation by increasing microbial lipopolysaccharide (LPS) and flagellin levels. <h3>Goal</h3> Examine if transient AIEC colonisation lastingly alters levels of LPS and flagellin and changes microbiota composition. <h3>Methods</h3> Germ-free mice (wild type (WT) and T5KO) were inoculated with AIEC strain LF82 and placed in standard housing allowing a complex microbiota that eliminated AIEC in both mice strains. Faeces were assayed for the inflammatory marker, lipocalin-2, bacterial loads, and microbiota composition by pyrosequencing. Faecal LPS and flagellin bioactivity were measured via a cell-based reporter assay. <h3>Results</h3> Transient AIEC colonisation, in WT mice, did not alter inflammatory markers, bacterial loads, microbiota composition, nor its pro-inflammatory potential. By contrast, transient AIEC colonisation of T5KO mice drove chronic inflammation which correlated with microbiota components having higher levels of bioactive LPS and flagellin. Such AIEC-induced elevation of LPS and flagellin persisted well beyond AIEC clearance, required AIEC be flagellated, and was associated with alteration in microbiota species composition including a loss of species diversity. <h3>Conclusions</h3> AIEC, and perhaps other pathobionts, may instigate chronic inflammation in susceptible hosts by altering the gut microbiota composition so as to give it an inherently greater ability to activate innate immunity/pro-inflammatory gene expression.
Effects of Ventilation with Different Positive End-expiratory Pressures on Cytokine Expression in the Preterm Lamb Lung
Authors: APURWA S. NAIK, SUHAS G. KALLAPUR, CINDY J. BACHURSKI, ALAN H. JOBE, JACEK MICHNA, BORIS W. KRAMER, MACHIKO IKEGAMI
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Ventilator-induced lung injury increases proinflammatory cytokines in the adult lung. We asked if positive end-expiratory pressure (PEEP) affects proinflammatory cytokine mRNA expression in the preterm lung. Preterm lambs at 129 ± 3 d gestation were treated with 100 mg/kg recombinant human surfactant protein-C surfactant and ventilated for 2 or 7 h with 0, 4, or 7 cm H2O of PEEP. Unventilated fetal lambs were used as controls. Within 2 h of ventilation, alveolar total protein and activated neutrophils were increased and expression of mRNAs for the proinflammatory cytokines interleukin (IL)-1 β , IL-6, IL-8, and tumor necrosis factor- α (TNF- α ) was increased in lung tissue of all ventilated animals relative to unventilated controls. Alveolar protein and neutrophils were higher for 0 and 7 PEEP animals than 4 PEEP animals. IL-1 β , IL-6, and IL-8 mRNAs were significantly elevated in animals ventilated with 0 PEEP compared with 4 PEEP. The percentage fractional area of collapsed alveoli was significantly higher for 0 PEEP compared with 4 and 7 PEEP groups. Mechanical ventilation increased the expression of proinflammatory mediators in surfactant-treated preterm lungs and the use of 4 PEEP minimized this response.Keywords: inflammation; lung injury; bronchopulmonary dysplasia; respiratory distress syndrome
Intraductal mono-octanoin for the direct dissolution of bile duct stones: experience in 343 patients.
Authors: K R Palmer, A F Hofmann
Journal: Gut (1986)

The efficacy and safety of mono-octanoin, a cholesterol solvent for the direct dissolution of stones in the biliary tract, was assessed by collating case reports on 343 patients provided by 222 physicians who used the material between 1977 and 1983. Most patients had previously undergone cholecystectomy, with common duct exploration, the majority within the preceding six weeks. In most, sphincterotomy was impossible or if carried out, had not induced stone passage. Stone dissolution was considered preferable to surgery, especially in patients who were frail, elderly, or had multiple medical problems. Treatment was unequivocally successful in 88 patients (26%) and was a valuable adjunct to interventional treatment in another 29 subjects (8%). In 70 patients (20%), calculi became smaller, but remained within the biliary tree. Thus, mono-octanoin was judged to have been useful in 54% of patients. Treatment was ineffective in 124 cases (36%). In the remaining 32 patients (9%), treatment was aborted because of side effects. Such side effects were common, occurring in 67% of cases, and in 41% of patients they were multiple. Abdominal pain was the most common complication. Other side effects reported were nausea, vomiting, and diarrhoea. Side effects were usually dose related and responded to reduction in infusion rate. Side effects were life threatening in 12 patients (5%), but there were no permanent sequelae and no deaths occurred. These data indicate that mono-octanoin is moderately effective, generally second line, but sometimes first line, treatment for retained biliary duct calculi.
On the Cutting Edge: Ethical Responsiveness to Cesarean Rates
Authors: Sylvia Burrow
Journal: The American Journal of Bioethics (2012)

Cesarean delivery rates have been steadily increasing worldwide. In response, many countries have introduced target goals to reduce rates. But a focus on target goals fails to address practices embedded in standards of care that encourage, rather than discourage, cesarean sections. Obstetrical standards of care normalize use of technology, creating an imperative to use technology during labor and birth. A technological imperative is implicated in rising cesarean rates if physicians or patients fear refusing use of technology. Reproductive autonomy is at stake since a technological imperative undermines patients' ability to choose cesareans or refuse use of technology increasing the likelihood of cesareans. To address practices driven by a technological imperative I outline three physician obligations that are attached to respecting patient autonomy. These moral obligations show that a focus on respect for autonomy may prove not only an ideal ethical response but also an achievable practical response to lowering cesarean rates.
STRUCTURAL BASIS OF T CELL RECOGNITION
Authors: K. Christopher Garcia, Luc Teyton, Ian A. Wilson
Journal: Annual Review of Immunology (1999)

▪ Abstract Exciting breakthroughs in the last two years have begun to elucidate the structural basis of cellular immune recognition. Crystal structures have been determined for full-length and truncated forms of αβ T cell receptor (TCR) heterodimers, both alone and in complex with their peptide-MHC (pMHC) ligands or with anti-TCR antibodies. In addition, a truncated CD8 coreceptor has been visualized with a pMHC. Aided in large part by the substantial body of knowledge accumulated over the last 25 years on antibody structure, a number of general conclusions about TCR structure and its recognition of antigen can already be derived from the relatively few TCR structures that have been determined. Small, but important, variations between TCR and antibody structures bear on their functional differences as well as on their specific antigen recognition requirements. As observed in antibodies, canonical CDR loop structures are already emerging for some of the TCR CDR loops. Highly similar docking orientations of the TCR Vα domains in the TCR/pMHC complex appear to play a primary role in dictating orientation, but the Vβ positions diverge widely. Similar TCR contact positions, but whose exact amino acid content can vary, coupled with relatively poor interface shape complementarity, may explain the flexibility and short half-lives of many TCR interactions with pMHC. Here we summarize the current state of this field, and suggest that the knowledge gap between the three-dimensional structure and the signaling function of the TCR can be bridged through a synthesis of molecular biological and biophysical techniques.
Tumor stem cells, notch, and the news
Authors: W. K. A. Yung
Journal: Neuro-Oncology (2010)

Tumor stem cells, notch, and the newsAs we prepared to put this issue of Neuro-Oncology to bed, we noted with interest that the topic of our review article this month, Notch signaling in human gliomas, is also in the news.In our case, we are running a review titled "The functional role of Notch signaling in human gliomas," by . 1 In this review, the authors look at the "interplay" between Notch signaling in normal glial development and processes known to be involved in the development of malignant tumors (for instance, hypoxia and angiogenesis).In particular, they look at the roles of Notch in normal neural stem cells and brain cancer stem cells, the latter of which represent a formidable therapeutic challenge (as stem cells do in all cancers 2 ).As Stockhausen et al. point out, therapies that can act at the stem cell level may offer the promise of overcoming gliomas' characteristic resistance to therapy and the consequently poor outcomes the patients face.The authors discuss several approaches of recent interest, including the use of gamma-secretase inhibitors to overcome the Notch signal.In the news, meanwhile, appeared an announcement from Duke University that the journal Stem Cells had posted a prepublication version of an article detailing Notch's contribution to the radioresistance of glioma stem cells and the use of gamma-secretase inhibitors to overcome that problem. 3 This example demonstrates the complexity of tumor progression and tumor cell differentiation and the necessity to better understand the multiple molecular signaling networks that exert control in this process.
Remarks on EMPYEMA THORACIS
Authors: H. M. Davies
Journal: BMJ (1931)

MLDICAL JOURNAL(not necessarily the rate) of the respirations.The, success Remarks of this compensation depends on the capacity of the ON individual to make the exertion and on the, size of -the EMPYEMA THORACI* opening into the pleural cavity.Failure means death byasphyxia.At the best, if the openling, into the pleural BY cavity is no bigger, than that of, the glottis, the intra- H. MORRISTOIN DAVIES, M.D., M.CH.CANTAB.pleural pressures will remain positive during eXDiiration F.R.C.S.ENG.but become negative during inspiration; tht -is to say,
The Evolving Relationship of Social Class to Tobacco Smoking and Lung Cancer
Authors: M. J. Thun
Journal: JNCI Journal of the National Cancer Institute (2009)

The article by Menvielle et al. ( 1 ) in this issue of the Journal fits into the epidemiological tradition of testing how well one scourge explains another.Its goal is to quantify the extent to which educational and socioeconomic differences in smoking in Western Europe account for social class differences in lung cancer occurrence.Complicating this effort, however, is that the relationships between social class, smoking, and lung cancer have not been static but have evolved over the last 50 years, following historical trends in the dissemination of manufactured cigarettes ( 2 ).In Europe, dependence on manufactured cigarettes spread from men to women, from North to South, and from higher to lower social classes ( 2 -4 ).Vestiges of this demographic progression can be seen in studies conducted early in the 20th century that showed no association between low socioeconomic status and higher risk of lung cancer ( 5 ).No disparity in lung cancer was seen among men in England and Wales in 1910 -1912 and 1930 -1932,
Management of Central Nervous System Lymphomas Using Monoclonal Antibodies: Challenges and Opportunities
Authors: Eric T. Wong
Journal: Clinical Cancer Research (2005)

Monoclonal antibodies (mAb) may change the management of central nervous system (CNS) lymphomas. This is due to the fact that traditional chemotherapies lack specificity for B-lymphoma cells and blood-brain barrier prevents adequate chemotherapy dosing in the CNS without significant systemic side effects. But in the past 5 years, the emergence of mAbs against specific receptors on B-lymphoma cells, either as a single agent or in combination with cytotoxic chemotherapies, may offer a better therapeutic index than conventional chemotherapies. The advantages of mAbs include high affinity to targets on lymphoma cells, their lack of pharmacodynamic or pharmacokinetic interactions with other drugs, and a potential for a synergistic therapeutic response when combined with conventional chemotherapies. Our review summarizes the biological behaviors of CNS lymphomas and the challenges and opportunities in using mAbs for CNS lymphomas.
ROYAL SOCIETY OF MEDICINE. JOINT MEETING OF THE SECTIONS OF DERMATOLOGY AND OCCUPATIONAL MEDICINE
Authors: F. R. Bettley
Journal: British Journal of Dermatology (1967)

Journal Article ROYAL SOCIETY OF MEDICINE. JOINT MEETING OF THE SECTIONS OF DERMATOLOGY AND OCCUPATIONAL MEDICINE Get access F. R. Bettley, Dr. F. R. Bettley, Dr. President of the Section of Dermatology Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 79, Issue 1, 1 January 1967, Pages 59–61, https://doi.org/10.1111/j.1365-2133.1967.tb11398.x Published: 01 January 1967
miR-99 Family of MicroRNAs Suppresses the Expression of Prostate-Specific Antigen and Prostate Cancer Cell Proliferation
Authors: Dandan Sun, Yong Sun Lee, Ankit Malhotra, Hak Kyun Kim, Mirela Matecic, Clive Evans, Roderick V. Jensen, Christopher A. Moskaluk, Anindya Dutta
Journal: Cancer Research (2011)

Abstract MicroRNAs (miRNA) have been globally profiled in cancers but there tends to be poor agreement between studies including in the same cancers. In addition, few putative miRNA targets have been validated. To overcome the lack of reproducibility, we profiled miRNAs by next generation sequencing and locked nucleic acid miRNA microarrays and verified concordant changes by quantitative RT-PCR. Notably, miR-125b and the miR-99 family members miR-99a, -99b, and -100 were downregulated in all assays in advanced prostate cancer cell lines relative to the parental cell lines from which they were derived. All four miRNAs were also downregulated in human prostate tumor tissue compared with normal prostate. Transfection of miR-99a, -99b, or -100 inhibited the growth of prostate cancer cells and decreased the expression of prostate-specific antigen (PSA), suggesting potential roles as tumor suppressors in this setting. To identify targets of these miRNAs, we combined computational prediction of potential targets with experimental validation by microarray and polyribosomal loading analysis. Three direct targets of the miR-99 family that were validated in this manner were the chromatin-remodeling factors SMARCA5 and SMARCD1 and the growth regulatory kinase mTOR. We determined that PSA is posttranscriptionally regulated by the miR-99 family members, at least partially, by repression of SMARCA5. Together, our findings suggest key functions and targets of miR-99 family members in prostate cancer suppression and prognosis. Cancer Res; 71(4); 1313–24. ©2011 AACR.
Changes in Corneal Topography after 25-Gauge Transconjunctival Sutureless Vitrectomy versus after 20-Gauge Standard Vitrectomy
Authors: F. Okamoto, C. Okamoto, N. Sakata, K. Hiratsuka, N. Yamane, T. Hiraoka, Y. Kaji, T. Oshika
Journal: Ophthalmology (2007)
Subcutaneous and intrahepatic growth of human hepatoblastoma in immunodeficient mice
Authors: J. Marco Schnater, Elisabeth Bruder, Sibylle Bertschin, Thomas Woodtli, Chiel de Theije, Torsten Pietsch, Daniel C. Aronson, Dietrich von Schweinitz, Wouter H. Lamers, Eleonore S. Köhler
Journal: Journal of Hepatology (2006)
From Developmental Origins of Adult Disease to Life Course Research on Adult Disease and Aging: Insights from Birth Cohort Studies
Authors: Chris Power, Diana Kuh, Susan Morton
Journal: Annual Review of Public Health (2013)

Maturation of long-running birth cohort studies has fostered a life course approach to adult health, function, and disease and related to conceptual frameworks. Using broad concepts of human development including physical, cognitive, and emotional function, birth cohorts provide insights into the processes across the life course and between generations that link to adult outcomes. We discuss findings on the determinants and health consequences of lifetime trajectories of body size, cognitive and emotional function, and socioeconomic position. Findings from the studies suggest that, for some adult health outcomes, explanations will be incomplete unless exposures and processes from across the life course are taken into account. New birth cohort studies are poised to delineate further the nature and timing of life course relationships in contemporary generations of children.