tbuckley/cabot-search huggingface dataset:
AB0042 Deletion of mpges-1 affects fatty acid composition and eicosanoid profiles in mice
Authors: H. Idborg, P. Olsson, P. Leclerc, J. Raouf, P.-J. Jakobsson, M. Korotkova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> mPGES-1 is considered an attractive alternative target for anti-inflammatory treatment with improved selectivity and safety compared to NSAIDs. Genetic deletion or pharmacological inhibition of mPGES-1 activity or expression down-regulate inflammation and pain in experimental models of arthritis. However, a detailed understanding of the molecular mechanisms and pathways affected by deletion/inhibition of mPGES-1 is essential before mPGES-1 inhibitors can safely be applied in the clinics. <h3>Objectives</h3> To investigate the effect of mPGES-1 deletion on the levels of bioactive lipid mediators such as the eicosanoids (down-stream cascade) and fatty acids (up-stream cascade). <h3>Methods</h3> Peritoneal macrophages (PM) from wild type (WT) and knock-out (mPGES-1-/-, KO) mice were induced with LPS for 16 h. Cells were harvested for gene expression analysis and supernatants were collected for eicosanoid analysis. Gene expression profiling in WT and KO macrophages was performed using the microarray analysis (Applied Biosystems). Eicosanoid profiling of approximately 30 compounds was performed using LC-MS/MS. Fatty acid composition of total lipids in spleen and brain homogenates of WT and KO mice were determined using GC/FID. <h3>Results</h3> Microarray analysis revealed that genetic deletion of mPGES-1 affected expression of genes related to lipid metabolism and mainly associated with eicosanoid, fatty acid and phospholipid metabolism, (e.g., Pla1A, Ptgis, Fabp3, Cept1, Comt etc). Compared to WT, mPGES-1 deficient PM displayed a markedly attenuated increase in PGE<sub>2</sub> production upon LPS stimulation, and exhibited significantly increased levels of PGD<sub>2</sub> metabolites such as 15-deoxy-Δ <sup>12,14</sup> PGJ<sub>2</sub> and 15-deoxy-Δ <sup>12,14</sup> PGD<sub>2</sub> (p&lt;0.05). There were significant differences in the fatty acid composition in spleen (e.g., palmitoleic acid decreased in KO, p&lt;0.05) and brain (e.g., myristic acid decreased in KO, p&lt;0.05) of KO and WT mice, suggesting that feed-back mechanisms are alternated by the deletion of m-PGES-1. <h3>Conclusions</h3> Data reveals that mPGES-1 deficient PMs displayed shunting towards PGD<sub>2</sub> pathway, i.e., towards anti-inflammatory metabolites, upon LPS stimulation compared to WT PMs. Moreover, mPGES-1 depletion alters the fatty acid composition of tissue lipids. These effects of inducible PGE<sub>2</sub> on lipid metabolism have important implications for future mPGES-1 inhibitors and deserve further investigation. <h3>Disclosure of Interest</h3> None Declared
Germany takes crisis measures to cap health spending
Authors: A. Tuffs
Journal: BMJ (2002)

Within weeks of re-election, the German health minister, Ulla Schmidt, is trying to stop the rapid increase in the health budget by introducing a bill of emergency measures

Health insurance companies face a deficit of several billion euros if her emergency actions fail. They would be forced to raise their fees in 2003, which would put an extra load on employers and might cause further unemployment.

Under her proposed bill, budgets …
Cellular signalling pathways mediating dilation of porcine pial arterioles to adenosine A2A receptor activation
Authors: Travis W. Hein, Wenjuan Xu, Yi Ren, Lih Kuo
Journal: Cardiovascular Research (2013)

AimsAdenosine is a potent vasodilator contributing to cerebral blood flow regulation during metabolic stress. However, the distribution of adenosine receptor subtypes and underlying signalling mechanisms for dilation of pial arterioles remain unclear. The present study aimed at addressing these issues.
Danazol and Non-Hodgkin's Malignant Lymphomas
Authors: L. DANEL
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 February 1987Danazol and Non-Hodgkin's Malignant LymphomasL. DANEL, M. RABA, P. BIRON, M. FAVROT, S. SAEZ, T. PHILIPL. DANELSearch for more papers by this author, M. RABASearch for more papers by this author, P. BIRONSearch for more papers by this author, M. FAVROTSearch for more papers by this author, S. SAEZSearch for more papers by this author, T. PHILIPSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-106-2-329_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Sex hormones appear to influence the immune system; for example, after immunization, women have higher immunoglobulin levels and a greater capacity for producing antibodies than men (1). The sex hormone modulation of cellular immune responses may be of pathophysiologic and perhaps therapeutic importance, because in the NZB/NZW/BFI mouse lupus model, castration of the male accelerates the disease and administration of estrogens to the castrated males accelerates the disease still further (2). Recently, we reported the presence of androgen receptors in 13 biopsy specimens of non-Hodgkin's malignant lymphomas (3). Because danazol is an impeded androgen and antiestrogen with...References1. EIDINGERGARRET DT. Studies of the regulatory effects of the sex hormones on antibody formation and stem cell differentiation. J Exp Med. 1972;136:1098-116. CrossrefMedlineGoogle Scholar2. ROUBINIANTALALGREENSPANGOODMANSLITERI JNJJP. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978;147:1568-83. CrossrefMedlineGoogle Scholar3. DANELMENOUNISEBBANMAGAUDSAEZ LMCJS. Characterization of a specific androgen receptor in non-Hodgkin's lymphoma cells. J Steroid Biochem. 1984;21:421-6. CrossrefMedlineGoogle Scholar4. MICHALSKIMCCOMBSROUBINIANTALA JCJN. Effects of androgen therapy on survival and suppressor cell activity in aged NZB/NZW F hybrid mice. Clin Exp Immunol. 1983;52:229-33. MedlineGoogle Scholar5. The Non-Hodgkin's Lymphomas Pathologic Classification Project: National Cancer Institute sponsored study of classification of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. Cancer. 1982;49:2112-8. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Centre Leon Berard 69373 Lyon Cedex 08 France PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1987Volume 106, Issue 2Page: 329-330KeywordsAndrogensAntibodiesBiopsyEstrogensImmune responseImmune systemLymphomaSex hormones Issue Published: 1 February 1987 PDF downloadLoading ...
POLIOMYELITIS DANGER IN TROPICAL AFRICA
Authors: O.O. Akinkugbe, T.I. Francis, G.B. Wyatt, I.F. Brockington, A.J.P. Willis, A. Brown, T.W.G. Kinnear, T.O. Ogunlesi, C. Nwokolo, A.C. Ikeme
Journal: The Lancet (1966)
A NOTE ON DISSEMINATED SCLEROSIS
Authors: F. Coates
Journal: BMJ (1930)

in 1903 had suggested that pre-natal tuiberculosis miglht in some cases posSibly be caused by the foetus swallowing liquior amnnii containing tubercle 'bacilli deriv-ed fromll a disintegrating lesioni of the placenta.How rare cases of ti ue congenital tuberculosis mnust be manv be jtlRgedl by the fact that in 1916 onie of us was able to summllnarize all the Litherto proved anid probable cases of trule conigeniittal tuber- 'ulosis in a short article published in thle British Jowurlial fC'h illrcn's Discascs.1'In ouir present paper it would plrllaps hav-e been better to lo.se the term " malignant melanomna " inistead of melan- otic sarcoma, as it might possiblly be suggested that the pl imary growth in the mother (the site of which is not ceirtaini) was a melano-tic carciomia.I'hle tui-mours in the child's liver w-ere obviouslyv of miultiple mietastatic type, annd it is the absence of any-pIriiiiaryt tuimouir ian the chlil-d thalt makes the case uiniqu;e, thle r eal primary growtlh hlavaiing been, of couirse, in the deatid m-iother.The inocula- tion of the-chilcd may hav-e takei l)lace llot loig before, or ("-evn at, birth.The liver, now in the museimiii of the Royal College of Suirgeons of England, was denionstrated by uis oni Fe(bruary 28tlh, at tho Section.for the Study of Disease in C'hiildrell, of the Royal Society of Medicine.
Clozapine, Diabetes Mellitus, Weight Gain, and Lipid Abnormalities: A Five-Year Naturalistic Study
Authors: David C. Henderson, Enrico Cagliero, Colin Gray, Rima A. Nasrallah, Doug L. Hayden, David A. Schoenfeld, Donald C. Goff
Journal: American Journal of Psychiatry (2000)

The goal of this 5-year naturalistic study of patients treated with clozapine was to examine the incidence of treatment-emergent diabetes mellitus in relation to other factors, including weight gain, lipid abnormalities, age, clozapine dose, and treatment with valproate.Data on age, gender, race, diagnosis, family history of diabetes, and age at clozapine initiation were collected from medical records of 82 outpatients with schizophrenia or schizoaffective disorder. Clozapine dose, data on use of valproate, and laboratory test results were recorded at 6-month intervals.The mean age at the time of clozapine initiation of the 82 patients was 36.4 years; 26.8% of the patients were women, and 91.5% were Caucasian. The mean baseline weight was 175.5 lb, and the mean body mass index was 26.9 kg/m(2). Thirty patients (36.6%) were diagnosed with diabetes during the 5-year follow-up. Weight gain, use of valproate, and total daily dose of clozapine were not significant risk factors for developing diabetes mellitus. Patients experienced significant weight gain that continued until approximately month 46 from initiation of clozapine. There was a nonsignificant increase in total serum cholesterol and a significant increase in serum triglycerides level.The results support the hypotheses that patients treated with clozapine experience significant weight gain and lipid abnormalities and appear to be at increased risk for developing diabetes.
[512] HEPATITIS B VIRUS MUTANTS IN PATIENTS FAILING ANTIRETROVIRALS WITH ANTI-HBV ACTIVITY: IMPLICATIONS FOR DIAGNOSTICS AND VACCINE ESCAPE
Authors: J. Sheldon, B. Ramos, J. Garcia-Samaniego, P. Rios, A. Bartholomeusz, M. Romero, S. Locarnini, V. Soriano
Journal: Journal of Hepatology (2007)
Carcinogenic Interactions Between Virus, Cell, and Organism
Authors: Harry Rubin
Journal: JAMA (1964)

IN STUDYING the role of viruses in cancer there are two paramount questions one must ask: what and where are the cancer viruses, and how do they work? Answering the first question involves isolating and identifying the tumor. It also involves showing how the viruses are distributed and perpetuated in nature. Much is known about the occurrence and transmission of tumor viruses of animals, other than humans, and certain selected aspects will be considered here. Answering the second question, however, is a more complex business. It requires a vast amount of detailed information about the relationship of the virus to the cell, and about those regulatory mechanisms of normal cells which are disrupted during the malignant transformation. Although something has been learned about these problems, the information available seems miniscule alongside that still to be gained. I shall therefore mention a few aspects of what we do not know as
Effect of 8 Weeks of Overfeeding on Ectopic Fat Deposition and Insulin Sensitivity: Testing the “Adipose Tissue Expandability” Hypothesis
Authors: Darcy L. Johannsen, Yourka Tchoukalova, Charmaine S. Tam, Jeffrey D. Covington, Wenting Xie, Jean-Marc Schwarz, Sudip Bajpeyi, Eric Ravussin
Journal: Diabetes Care (2014)

The presence of large subcutaneous adipocytes in obesity has been proposed to be linked with insulin resistance and type 2 diabetes through the "adipose tissue expandability" hypothesis, which holds that large adipocytes have a limited capacity for expansion, forcing lipids to be stored in nonadipose ectopic depots (skeletal muscle, liver), where they interfere with insulin signaling. This hypothesis has, however, been largely formulated by cross-sectional findings and to date has not been prospectively demonstrated in the development of insulin resistance in humans.Twenty-nine men (26.8 ± 5.4 years old; BMI 25.5 ± 2.3 kg/m(2)) were fed 40% more than their baseline requirement for 8 weeks. Before and after overfeeding, insulin sensitivity was determined using a two-step hyperinsulinemic-euglycemic clamp. Intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) were measured by (1)H-MRS and abdominal fat by MRI. Subcutaneous abdominal adipose and skeletal muscle tissues were collected to measure adipocyte size and markers of tissue inflammation.Subjects gained 7.6 ± 2.1 kg (55% fat) and insulin sensitivity decreased 18% (P < 0.001) after overfeeding. IHL increased 46% from 1.5% to 2.2% (P = 0.002); however, IMCL did not change. There was no association between adipocyte size and ectopic lipid accumulation. Despite similar weight gain, subjects with smaller fat cells at baseline had a greater decrease in insulin sensitivity, which was linked with upregulated skeletal muscle tissue inflammation.In experimental substantial weight gain, the presence of larger adipocytes did not promote ectopic lipid accumulation. In contrast, smaller fat cells were associated with a worsened metabolic response to overfeeding.
Treatment of hypertension with ketanserin, a new selective 5-HT2 receptor antagonist.
Authors: G J Wenting, A J Man in 't Veld, A J Woittiez, F Boomsma, M A Schalekamp
Journal: BMJ (1982)

The new selective 5-HT2 receptor blocking agent ketanserin was given in a dose of 10 mg intravenously to 12 patients with essential hypertension. It caused a distinct fall in supine systemic arterial, right atrial, pulmonary artery, and pulmonary capillary "wedge" pressures. Cardiac output, renal blood flow, and glomerular filtration rate showed no persistent changes. Thus 5-HT2 receptor blockade caused dilatation of both resistance and capacitance vessels and of the renal vascular bed. Heart rate and plasma concentrations of renin and noradrenaline rose after ketanserin. These data suggest that 5-HT may have a role in maintaining high blood pressure.
Treeness Triangles: Visualizing the Loss of Phylogenetic Signal
Authors: WT White, SF Hills, R Gaddam, BR Holland, David Penny
Journal: Molecular Biology and Evolution (2007)

It is well known that molecular data "saturates" with increasing sequence divergence (thereby losing phylogenetic information) and that in addition the accumulation of misleading information due to chance similarities or to systematic bias may accompany saturation as well. Exploratory data analysis methods that can quantify the extent of signal loss or convergence for a given data set are scarce. Such methods are needed because genomics delivers very long sequence alignments spanning substantial phylogenetic depth, where site saturation may be compounded by systematic biases or other alternative signals. Here we introduce the Treeness Triangle (TT) graph, in which signals detectable by Hadamard (spectral) analysis are summed into 3 categories--those supporting 1) external and 2) internal branches in the optimal tree, in addition to 3) the residuals (potential internal branches not present in the optimal tree). These 3 values are plotted in a standard ternary coordinate system. The approach is illustrated with simulated and real data sets, the latter from complete chloroplast genomes, where potential problems of paralogy or lateral gene acquisition can be excluded. The TT uncovers the divergence-dependent loss of phylogenetic signal as subsets of chloroplast genomes are investigated that span increasingly deeper evolutionary timescales. The rate of signal loss (or signal retention) varies with the gene and/or the method of analysis.
Insights into defibrotide as therapy for veno-occlusive disease
Authors: Jennifer R. Gamble, Mathew A. Vadas, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2009)

Defibrotide (DF) is a mixture of porcine-derived single-stranded phosphodiester oligonucleotides (9-80-mer; average, 50-mer) that has been successfully used to treat severe hepatic veno-occlusive disease (sVOD) with multiorgan failure (MOF) in patients who have received cytotoxic chemotherapy in preparation for bone marrow transplantation. However, its mechanism of action is unknown. Herein, we show that DF and phosphodiester oligonucleotides can bind to heparin-binding proteins (eg, basic fibroblast growth factor [bFGF] but not vascular endothelial growth factor [VEGF] 165) with low nanomolar affinity. This binding occurred in a length- and concentration-dependent manner. DF can mobilize proangiogenic factors such as bFGF from their depot or storage sites on bovine corneal endothelial matrix. However, these molecules do not interfere with high-affinity binding of bFGF to FGFR1 IIIc but can replace heparin as a required cofactor for binding and hence cellular mitogenesis. DF also protects bFGF against digestion by trypsin and chymotrypsin and from air oxidation. In addition, DF binds to collagen I with low nanomolar affinity and can promote human microvascular endothelial cell-1 (HMEC-1) cell mitogenesis and tubular morphogenesis in three-dimensional collagen I gels. Thus, our data suggest that DF may provide a stimulus to the sinusoidal endothelium of a liver that has suffered a severe angiotoxic event, thus helping to ameliorate the clinical sVOD/MOF syndrome.
The Role of the Mouse Y Chromosome on Susceptibility to Testicular Germ Cell Tumors
Authors: Philip D. Anderson, Man-Yee Lam, Christophe Poirier, Colin E. Bishop, Joseph H. Nadeau
Journal: Cancer Research (2009)

Abstract Testicular germ cell tumors (TGCT) are sex limited, occurring only in males with a Y chromosome. Recently, the gr/gr deletion on the human Y chromosome was associated with increased risk of TGCTs. In addition, the presence of Y chromosome sequences is associated with TGCTs in cases of gonadal dysgenesis. TGCTs in strain 129 males recapitulate many aspects of testicular cancer in human infants and can be used to evaluate the role of the Y chromosome in TGCT risk. We used chromosome substitution strains and a sex-reversing mutant to test the role of the Y chromosome on TGCT susceptibility. Our results show that a Y-linked gene that does not differ among the tested strains is essential for tumorigenesis. [Cancer Res 2009;69(8):3614–8]
Occurrence and Potential Human-Health Relevance of Volatile Organic Compounds in Drinking Water from Domestic Wells in the United States
Authors: Barbara L. Rowe, Patricia L. Toccalino, Michael J. Moran, John S. Zogorski, Curtis V. Price
Journal: Environmental Health Perspectives (2007)

As the population and demand for safe drinking water from domestic wells increase, it is important to examine water quality and contaminant occurrence. A national assessment in 2006 by the U.S. Geological Survey reported findings for 55 volatile organic compounds (VOCs) based on 2,401 domestic wells sampled during 1985-2002.We examined the occurrence of individual and multiple VOCs and assessed the potential human-health relevance of VOC concentrations. We also identified hydrogeologic and anthropogenic variables that influence the probability of VOC occurrence.The domestic well samples were collected at the wellhead before treatment of water and analyzed for 55 VOCs. Results were used to examine VOC occurrence and identify associations of multiple explanatory variables using logistic regression analyses. We used a screening-level assessment to compare VOC concentrations to U.S. Environmental Protection Agency maximum contaminant levels (MCLs) and health-based screening levels.We detected VOCs in 65% of the samples; about one-half of these samples contained VOC mixtures. Frequently detected VOCs included chloroform, toluene, 1,2,4-trimethylbenzene, and perchloroethene. VOC concentrations generally were < 1 microg/L. One or more VOC concentrations were greater than MCLs in 1.2% of samples, including dibromochloropropane, 1,2-dichloropropane, and ethylene dibromide (fumigants); perchloroethene and trichloroethene (solvents); and 1,1-dichloroethene (organic synthesis compound).Drinking water supplied by domestic wells is vulnerable to low-level VOC contamination. About 1% of samples had concentrations of potential human-health concern. Identifying factors associated with VOC occurrence may aid in understanding the sources, transport, and fate of VOCs in groundwater.
Standards of care for occupational asthma
Authors: S. M Tarlo
Journal: Thorax (2008)

suggestive evidence that b 2 adrenergic therapy might be able to enhance alveolar lung epithelial repair.The results of this study are important.They provide a new mechanism to potentially explain the beneficial effects of b 2 adrenergic agonist therapy in patients with acute lung injury.The data suggest that repair of the injured alveolus might be accelerated by b 2 agonists, an effect that could provide a functional epithelial barrier that might be better able to remove alveolar oedema fluid in patients with acute lung injury.Although not tested in this study, other investigators have suggested that b 2 adrenergic agonists might also decrease injurious inflammatory responses 17 and reduce lung endothelial injury. 18n summary, the investigators should be commended for an elegant translational study that tests a novel mechanism by which b 2 agonists might benefit the injured lung.Large well powered randomised clinical trials are needed to test the potential value of b 2 agonist therapy in patients with acute lung injury.In the USA, treatment with aerosolised b 2 agonist is currently being tested in a 1000 patient trial by the ARDS Network supported by the National Heart Lung and Blood Institute.Hopefully, a trial of intravenous salbutamol will be carried out with the support of the Medical Research Council in the UK in the near future.
A single practice's experience of NHS 111
Authors: M. O. Thompson, R. C. M. Jones
Journal: BMJ (2014)

The joint report discussed by Iacobucci says that NHS 111 and equivalent telephone advice services may help to reduce the pressures on the urgent and emergency care system.1 The general feeling is that the NHS 111 service has only served to increase pressure on already overstretched urgent care services, particularly ambulances and emergency departments.2 3 4 

To assess how the service works in our small inner city practice (n=2611), we reviewed all …
Point mutation in the gene encoding p300 suppresses thrombocytopenia in Mpl−/− mice
Authors: Maria Kauppi, James M. Murphy, Carolyn A. de Graaf, Craig D. Hyland, Kylie T. Greig, Donald Metcalf, Adrienne A. Hilton, Nicos A. Nicola, Benjamin T. Kile, Douglas J. Hilton, Warren S. Alexander
Journal: Blood (2008)