tbuckley/cabot-search huggingface dataset:
Blood levels and renal effects of atrial natriuretic peptide in normal man.
Authors: P Weidmann, L Hasler, M P Gnädinger, R E Lang, D E Uehlinger, S Shaw, W Rascher, F C Reubi
Journal: Journal of Clinical Investigation (1986)

Since mammalian atria were recently found to contain vasoactive and natriuretic peptides, we investigated the following in normal humans: plasma human atrial natriuretic peptide concentrations, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary water and electrolyte excretion, blood pressure (BP), and catecholamine, antidiuretic hormone (ADH), angiotensin II, and aldosterone levels before, during, and after intravenous administration of the newly synthetized alpha-human atrial natriuretic peptide (alpha hANP). In 10 subjects alpha hANP given as an initial bolus of 50 micrograms followed by a 45-min maintenance infusion at 6.25 micrograms/min increased plasma alpha hANP from 58 +/- 12 to 625 +/- 87 (mean +/- SEM) pg/ml; caused an acute fall in diastolic BP (-12%, P less than 0.001) and a hemoconcentration (hematocrit +7%, P less than 0.01) not fully explained by a negative body fluid balance; increased GFR (+15%, P less than 0.05) despite unchanged or decreased ERPF (filtration fraction +37%, P less than 0.001); augmented (P less than 0.05- less than 0.001) urinary chloride (+317%), sodium (+224%), calcium (+158%), magnesium (+110%), phosphate excretion (+88%), and free water clearance (from -0.76 to +2.23 ml/min, P less than 0.001) with only little change in potassium excretion; and increased plasma norepinephrine (P less than 0.001) while plasma and urinary epinephrine and dopamine, and plasma ADH, angiotensin II, and aldosterone levels were unchanged. The magnitude and pattern of electrolyte and water excretion during alpha hANP infusion could not be accounted for by increased GFR alone. Therefore, in normal man, endogenous alpha hANP seems to circulate in blood. alpha hANP can cause a BP reduction and hemoconcentration which occur, at least in part, independently of diuresis and are accompanied by sympathetic activation. An increase in GFR that occurs in the presence of unchanged or even decreased total renal blood flow is an important but not sole mechanism of natriuresis and diuresis induced by alpha hANP in man.
An Integrated View of Molecular Coevolution in Protein-Protein Interactions
Authors: S. C. Lovell, D. L. Robertson
Journal: Molecular Biology and Evolution (2010)

Protein–protein interactions effectively mediate molecular function. They are the result of specific interactions between protein interfaces and are maintained by the action of evolutionary pressure on the regions of the interacting proteins that contribute to binding. For the most part, selection restricts amino acid replacements, accounting for the conservation of binding interfaces. However, in some cases, change in one protein will be mitigated by compensatory change in its binding partner, maintaining function in the face of evolutionary change. There have been several attempts to use correlations in sequence evolution to predict interactions of proteins. Most commonly, these approaches use the entire sequence to identify correlations and so infer probable binding. However, other factors such as shared evolutionary history and similarities in the rates of evolution confound these whole-sequence–based approaches. Here, we discuss recent work on this topic and argue that both site-specific coevolutionary change and whole-sequence evolution contribute to evolutionary signals in sets of interacting proteins. We discuss the relative effects of both types of selection and how they might be identified. This permits an integrated view of protein–protein interactions, their evolution, and coevolution.
The Capsella rubella genome and the genomic consequences of rapid mating system evolution
Authors: Tanja Slotte, Khaled M Hazzouri, J Arvid Ågren, Daniel Koenig, Florian Maumus, Ya-Long Guo, Kim Steige, Adrian E Platts, Juan S Escobar, L Killian Newman, Wei Wang, Terezie Mandáková, Emilio Vello, Lisa M Smith, Stefan R Henz, Joshua Steffen, Shohei Takuno, Yaniv Brandvain, Graham Coop, Peter Andolfatto, Tina T Hu, Mathieu Blanchette, Richard M Clark, Hadi Quesneville, Magnus Nordborg, Brandon S Gaut, Martin A Lysak, Jerry Jenkins, Jane Grimwood, Jarrod Chapman, Simon Prochnik, Shengqiang Shu, Daniel Rokhsar, Jeremy Schmutz, Detlef Weigel, Stephen I Wright
Journal: Nature Genetics (2013)

Stephen Wright, Detlef Weigel and colleagues report the whole-genome sequence of Capsella rubella, a highly selfing crucifer found throughout much of southern and western Europe. They compare mixed-stage flower bud transcriptomes from C. rubella and C. grandiflora, finding a shift in expression of genes associated with flowering phenotypes and providing insights into the transition to selfing. The shift from outcrossing to selfing is common in flowering plants1,2, but the genomic consequences and the speed at which they emerge remain poorly understood. An excellent model for understanding the evolution of self fertilization is provided by Capsella rubella, which became self compatible <200,000 years ago. We report a C. rubella reference genome sequence and compare RNA expression and polymorphism patterns between C. rubella and its outcrossing progenitor Capsella grandiflora. We found a clear shift in the expression of genes associated with flowering phenotypes, similar to that seen in Arabidopsis, in which self fertilization evolved about 1 million years ago. Comparisons of the two Capsella species showed evidence of rapid genome-wide relaxation of purifying selection in C. rubella without a concomitant change in transposable element abundance. Overall we document that the transition to selfing may be typified by parallel shifts in gene expression, along with a measurable reduction of purifying selection.
Use of charcoal haemoperfusion in the management of severely poisoned patients.
Authors: J A Vale, A J Rees, B Widdop, R Goulding
Journal: BMJ (1975)

The clinical use of uncoated charcoal haemoperfusion systems, despite their efficacy, has hitherto been prevented by the occurrence of a number of adverse effects including charcoal embolism and marked thrombocytopenia. Charcoal coated with a synthetic hydrogel overcomes many of the disadvantages associated with the use of uncoated material in that there is a much reduced thrombocytopenia and no evidence of charcoal embolism. Six patients, severely poisoned as a result of overdoses of either a barbiturate or glutethimide, were haemoperfused using such a system. Four made complete recoveries, and the two patients who died had both suffered cardiorespiratory arrests before perfusion. In contrast to haemodialysis charcoal haemoperfusion is simple to initiate, less expensive in terms of manpower and equipment, and gives superior clearance data for all barbiturates and glutethimide. We believe that this technique may have a significant role to play in the management of the severely poisoned patient.
Lipid Mobilizer Hormone in Cobalt Chloride Hyperlipemia
Authors: Chris J. D. Zarafonetis, Robert H. Bartlett, Gerald L. Brody
Journal: JAMA (1965)

A lipid-mobilizing hormone (LM) was discovered in the plasma of man and other species by Seifter and Baeder 1 in 1954. These investigators later isolated LM from the posterior pituitary gland of hogs 2 and demonstrated that the plasma content of LM is greatly increased by the administration of cortisone and by subjecting animals to various stresses. 1,3 LM exerts two major effects: (1) it mobilizes fatty acids from the omental and mesenteric depots, and (2) it inhibits the delactescent action of heparin-clearing factor in vitro. Extensive clinical and laboratory studies have shown LM to be involved in the elevation of blood lipids which occurs consequent to surgical stress, 4,6 pregnancy, 5 and nephrosis, 1 as well as in hereditary hyperlipemias. 4 In addition, the hyperlipemias induced by protamine 7 and by diisopropyl fluorophosphate 7 appear to be mediated by the LM mechanism.  This investigation was done to determine whether
Variants in<i>ABCB1</i>,<i>TGFB1</i>, and<i>XRCC1</i>genes and susceptibility to viral hepatitis A infection in Mexican Americans
Authors: Lyna Zhang, Ajay Yesupriya, Dale J. Hu, Man-huei Chang, Nicole F. Dowling, Renée M. Ned, Venkatachalam Udhayakumar, Mary Lou Lindegren, Yury Khudyakov
Journal: Hepatology (2011)

Hepatitis A vaccination has dramatically reduced the incidence of hepatitis A virus (HAV) infection, but new infections continue to occur. To identify human genetic variants conferring a risk for HAV infection among the three major racial/ethnic populations in the United States, we assessed associations between 67 genetic variants (single nucleotide polymorphisms [SNPs]) among 31 candidate genes and serologic evidence of prior HAV infection using a population-based, cross-sectional study of 6,779 participants, including 2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, and 2,065 Mexican Americans enrolled in phase 2 (1991-1994) of the Third National Health and Nutrition Examination Survey. Among the three racial/ethnic groups, the number (weighted frequency) of seropositivity for antibody to HAV was 958 (24.9%), 802 (39.2%), and 1540 (71.5%), respectively. No significant associations with any of the 67 SNPs were observed among non-Hispanic whites or non-Hispanic blacks. In contrast, among Mexican Americans, variants in two genes were found to be associated with an increased risk of HAV infection: TGFB1 rs1800469 (adjusted odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.68; P value adjusted for false discovery rate [FDR-P] = 0.017) and XRCC1 rs1799782 (OR, 1.57; 95% CI, 1.27-1.94; FDR-P = 0.0007). A decreased risk was found with ABCB1 rs1045642 (OR, 0.79; 95% CI, 0.71-0.89; FDR-P = 0.0007).
NT-39 * GLUTAMINASE-MEDIATED METABOLIC PATHWAY INVOLVES GLIOBLASTOMA RESISTANCE TO mTOR-TARGETED THERAPIES
Authors: K. Tanaka, T. Sasayama, Y. Irino, K. Takata, H. Nagashima, K. Masui, B. Gini, H. Yang, P. S. Mischel, E. Kohmura
Journal: Neuro-Oncology (2014)

BACKGROUND: Although the phosphatidylinositol 3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) pathway is a master regulator of aerobic glycolysis and cellular biosynthesis, the effect of modulating mTOR activity on other metabolic processes, such as glutamine metabolism is not well understood. AIMS: Through an integrated analysis of glioblastoma (GBM) cell lines and clinical samples, we examined the importance of glutamine metabolism during mTOR-targeted treatments. METHODS: To identify metabolic response to mTOR-targeted treatments in GBM cells, we analyzed metabolites using gas chromatography and mass spectroscopy (GC/MS) in mutated EGFR (EGFRvIII)-expressing GBM cells treated with the mTOR inhibitors (rapamycin or PP242) and examined gene expression of key enzymes for glycolysis and glutaminolysis pathways using RT-PCR methods. RESULTS: Principal component analysis (PCA) based on GC/MS studies identified glutamic acid (glutamate), aspartic acid, citric (or isocitric) acid and succinic acid as key differentiating metabolites between control and mTOR-targeted treatment groups. Gene expression analysis identified upregulation of glutaminase (GLS) to generate glutamate from glutamine after mTOR inhibitor treatments, as well as downregulation of glycolytic enzymes. Importantly suppression of GLS activity with RNA interference or an inhibitor with Compound 968 sensitized U87/EGFRvIII cells to mTOR-targeted therapy through alpha-ketoglutarate (α-KG). CONCLUSIONS: The mTOR-targeted treatments affected glutamine utilization and elicited a switch in the pathways used to deliver glutamine carbon to the tricarboxylic acid (TCA) cycle, with increasing GLS expression. These results may suggest the new therapeutic strategies targeting GLS will be a rational approach in combination with mTOR-targeted therapy.
Salmonella Derby Infections in the Hospital.
Authors: Frank J. Sweeney
Journal: Annals of Internal Medicine (1964)

s1 April 1964Salmonella Derby Infections in the Hospital.Frank J. Sweeney Jr., M.D. (Associate), Eileen L. Randall, Ph.D., Kristine K. Knisely, M.D., W. Eugene Sanders, M.D., John F. Boring, Ph.D., Eli A. Friedman, M.D.Frank J. Sweeney Jr., M.D. (Associate)Search for more papers by this author, Eileen L. Randall, Ph.D.Search for more papers by this author, Kristine K. Knisely, M.D.Search for more papers by this author, W. Eugene Sanders, M.D.Search for more papers by this author, John F. Boring, Ph.D.Search for more papers by this author, Eli A. Friedman, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-4-734_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this report is to describe the characteristics of an outbreak of infection due to Salmonella derby which occurred in a large general hospital during a 7-month period and involved over 400 patients and employees.Epidemiological evidence suggests that infection in the early cases may have resulted from food contamination, however, subsequent cases conformed to an epidemiological pattern more like that seen in hospital cross infection with the streptococcus or staphylococcus. Data will be presented to show that the primary cases occurred in a highly susceptible patient population (gastrointestinal or malignant oncologic disease) and then spread person-to-person either... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Brooklyn, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1964Volume 60, Issue 4Page: 734-734KeywordsFoodSalmonellaStaphylococcal infectionStaphylococcusStreptococcal infectionsStreptococcus Issue Published: 1 April 1964 PDF DownloadLoading ...
A piece of my mind. Savannah River Parkway
Authors: A. O. Goldstein
Journal: JAMA (1989)

Officially it's called the Savannah River Plant, or SRP. Many call it the bomb factory. It is located 15 miles east of Augusta, Ga, where I live and work. Most people know little of what occurs there every day, despite the fact that SRP is responsible for the manufacture of virtually all the nuclear weapons materials in our country. Covering more than 600 square miles of land, the facility is tremendous. I drive through SRP occasionally, usually on my way to the beach. Highway 125 takes you through the heart of the complex for 20 miles. The early sun beams brightly through the windshield, promising a day of the childhood frolicking, corebody warming, and spiritual nourishment that occur only with ocean sounds. Yet, for 20 minutes, silent nuclear sounds eclipse the sun, waiting for an exit reprieve. The signs, buildings, roads, and security personnel offer small reality reminders, standing in
Pro-Inflammatory and T Cell Inhibitory Cytokines Are Secreted at High Levels in Tumor Cell Cultures of Human Renal Cell Carcinoma
Authors: Michael Lahn, Paul Fisch, Gabriele K&ouml;hler, Regina Kunzmann, Iris Hentrich, Heike Jesuiter, Dirk Behringer, Birgit Muschal, Hendrik Veelken, Peter Kulmburg, David N. Ikl&eacute;, Albrecht Lindemann
Journal: European Urology (1999)
The Role of Nutrition in Medicine
Authors: Norbert Freinkel
Journal: JAMA (1978)

IN HIS 1913 address to the New York Academy of Medicine, Lusk<sup>1</sup>defined nutrition as follows: The workshops of life require fuel to maintain them, and a necessary function of nutrition is to furnish fuel to the organism that the motions of life continue. Furthermore, the workshops of life are in a constant state of partial breaking down and materials must be furnished to repair the worn-out parts. In the fuel factor and the repair factor lie the essence of the science of nutrition. Benedict<sup>2</sup>extended the definition to include the traffic in endogenous as well as exogenous fuels. Thus, in the 1915 account of his study of prolonged fasting, he wrote: In the normal life of man, the demands for nutrition are usually met by periodic feeding. When the demands are not met, body reserves must be drawn upon.... It is to study these problems that observations
A8.18 Human CD141<sup>+</sup>dendritic cells are present at the site of inflammation in arthritis and promote the inflammatory process via IFN lambda
Authors: M I Ramos, T H Ramwadhdoebe, R de Groot, B Helder, M B M Teunissen, D van der Coelen, E C de Jong, P P Tak, M C Lebre
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background and Objectives</h3> Dendritic cells (DCs) are a heterogeneous population of antigen-presenting cells, crucial for the initiation and regulation of adaptive immunity, but also critical for the maintenance of both central and peripheral tolerance. However, remarkably little is known regarding the distribution, phenotype, maturation status, and functional profile of migratory DC populations in inflamed tissues and in particular in chronic autoimmune diseases. In this study we aimed to characterise the DC subsets and the nature of their <i>in situ</i> functional profile at the site of inflammation in arthritis. <h3>Materials and Methods</h3> Single-cell suspensions from paired peripheral blood mononuclear cells (PBMC), synovial fluid mononuclear cells (SFMC) and Lymph node (LN) samples were stained with DC surface markers and analysed by flow cytometry (FACS). Immunohistochemical and double immunofluorescent stainings were performed for identification of the different DC subsets (CD1c<sup>+</sup>, CD304<sup>+</sup> and CD141<sup>+</sup> DCs) IFN λ (IL-29) and IL-29-producing cells. IFN λ receptor (IL-28RA), IFN λ (both IL-28 and IL-29), CxCL10 gene expression (mRNA) in synovial tissue (ST) from RA and PsA patients, and CXCL10 induced by IL-29 in RA and healthy donor T cells was assessed by qPCR. IL-28RA protein expression levels on T cells was analysed by western blot. <h3>Results</h3> We reported for the first time that CD141<sup>+</sup> DCs, human homologues of mouse CD8<sup>+</sup>a DCs, are present at the site of inflammation in arthritis. These cells were present in blood, synovial fluid and ST of RA and PsA patients, RA LNs and lesional skin from PsA patients. FACS analysis revealed that these cells are increased in SFMCs compared to paired PBMCs in RA and PsA. We showed that IFN-l1 (IL-29) and IFN-l2 (IL-28A) are expressed in RA and PsA ST both at mRNA and protein level. We identified CD141<sup>+</sup>DCs, CD304<sup>+</sup> DCs and CD31<sup>+</sup> endothelial/monocytes as the major IL-29 producers in ST. We observed IL-28RA expression in RA and PsA ST and identified IL-28RA<sup>+</sup> T cells in close proximity with IL-29-producing cells in RA tissue suggesting a possible interaction. T cells upregulated CXCL10 gene expression upon stimulation with recombinant IL-29. Interestingly, IL-29-induced CXCL10 could be inhibited by blocking Jak/STAT pathway. <h3>Conclusions</h3> Studying the role of different DCs subsets in autoimmunity might provide new insights for the understanding of the inflammatory process in arthritis. Targeting specific DC subsets rather than general DC depletion might be a new and effective therapeutic strategy in arthritis.
Increased Risk of Group B Streptococcal Disease in Twins
Authors: Morven S. Edwards
Journal: JAMA (1981)

Infants who are the products of multiple births comprise a newly defined group of patients at increased risk for the development of invasive, group B streptococcal infection. This report summarizes the clinical and bacteriologic features of 11 sets of twins and one set of triplets in which one (nine sets) or more (three sets) infants had proved early- or late-onset group B streptococcal infection. Reasons for the enhanced susceptibility of index patients and their siblings are discussed. On the basis of these observations, an empirical approach is proposed for the treatment of the apparently noninvolved sibling of a twin with invasive group B streptococcal infection. (<i>JAMA</i>1981;245:2044-2046)
Health Insurance for Children — A Model for Incremental Health Reform?
Authors: Peter P. Budetti
Journal: New England Journal of Medicine (1998)

In this issue of the Journal, Newacheck and colleagues1 present new evidence confirming that children from families without health insurance are far less likely to get medical care when they need it, or to get regular care from physicians in their offices, in private clinics, or at health maintenance organizations. Moreover, although racial, income, and other barriers persist, being uninsured is a powerful independent predictor of reduced access to care, and the principal reason families have no coverage is their inability to pay for it. Commenting forcefully on the United States' unique and persistent tolerance of this situation, Uwe Reinhardt . . .
Abstract B18: Induction of Th1/Th17 and inhibition of Th3 cellular profile by DC-based immunotherapy is associated with immunological and clinical anti-tumor responses in melanoma patients
Authors: Claudia Durán, Gabriela Segal, Lorena Salazar, Cristián Pereda, Tempio Fabián, Flavio Salazar-Onfray, Mercedes N. López
Journal: Clinical Cancer Research (2010)

Abstract The ability of DCs to induce a primary immune response makes them ideal candidates for cancer vaccines against tumors. Recently, in a serie of phase I/II clinical studies, we showed the effectiveness of autologous DCs loaded with a conditioned allogeneic melanoma cell lysate named TRIMEL. Our results demonstrated a correlation between positive tumor-specific delayed type hypersensitivity (DTH) reaction induced by DC-vaccination, and improved long-term patient survival in late-stage melanoma patients. In fact, 60% of patients showed a positive DTH reaction showing a three-fold prolonged survival compared to non-responder patients (33 and 11 months respectively). Herein, we investigated whether cellular and cytokine profiles in patients PBL before and after vaccination reflects differential responses associated to the clinical outcome. Analysis of T cell populations in blood showed that melanoma patients (n=28) have an increased proportion of Th3 (CD4+TGF-β+) regulatory T lymphocytes (2.64 % ± 0.16) compared to normal donors (n=14) (1.72 % ± 0.22). However, we didn't observed differences in TGF-β concentrations at serum level. Moreover, we analyzed vaccine effect on cytokine and cellular responses in PBL. Interestling, although there was not differences in Th3 population proportions between responder (n=14) and non-responder patients (n=14) before vaccination, after treatment responder patients showed a three-fold reduction of CD4+TGf-β+ T cells compared to non-responders (1.65 % ± 0.19 and 5.54 % ± 0.28 respectively). Furthermore, our results show that DC-vaccination resulted in a three-fold augment of IFN-γ releasing by Th1 population and a two-fold increase of IL-17 producing Th17 lymphocyte population in responder patients, but not in non-responders. A direct correlation between IFN-γ and IL-17 production in responder patients blood was observed (p &amp;lt; 0.0001) suggesting that those cytokines may favour an anti melanoma response. Taken together our results indicates that despite undetectable differences in the cellular and cytokine profiles in melanoma patients before DC-vaccination, immunization resulted in two different pattern of response associated to the immunological and clinical outcome. Our study may contribute to a better understanding of clinical immunological responses and to an earlier prognosis of patient outcome. Citation Information: Clin Cancer Res 2010;16(7 Suppl):B18