tbuckley/cabot-search huggingface dataset:
Therapeutic Vaccination against Murine Lymphoma by Intratumoral Injection of Naive Dendritic Cells
Authors: Wenru Song, Ronald Levy
Journal: Cancer Research (2005)

Abstract Dendritic cells are potent antigen-presenting cells that can induce both immune responses and tolerance depending on their state of activation. Immunologic tolerance to established tumors is a major impediment for the development of effective cancer immunotherapy. Dendritic cells may be deficient in number or in function at the tumor site. To address this problem, we evaluated the ability of immature naïve dendritic cells to induce an antitumor immune response when injected directly into a murine B-cell lymphoma. Mice with advanced transplanted syngeneic tumor were given intratumoral injections of bone marrow–derived dendritic cells. Intratumoral dendritic cell injection alone had no antitumor effect. Systemic chemotherapy alone resulted in only transient tumor regression. However, the intratumoral injection of dendritic cells after chemotherapy led to complete, long-term tumor regression in the majority of treated mice. This dendritic cell–mediated antitumor effect was systemic, resulting in simultaneous elimination of the tumor at second uninjected sites. In addition, it resulted in long-term memory with resistance to tumor rechallenge. Both CD4+ and CD8+ T cells are necessary for the antitumor effect. Furthermore, tumors that occasionally recurred in mice with initial complete tumor regression could be retreated by the same combined chemoimmunotherapy approach. These results show that immunotherapy can succeed in the setting of advanced lymphoma if dendritic cells are restored and loaded with tumor antigens in situ at a single tumor site.
Processing of a Multiple Membrane Spanning Epstein-Barr Virus Protein for Cd8+T Cell Recognition Reveals a Proteasome-Dependent, Transporter Associated with Antigen Processing–Independent Pathway
Authors: Georg Lautscham, Sabine Mayrhofer, Graham Taylor, Tracey Haigh, Alison Leese, Alan Rickinson, Neil Blake
Journal: The Journal of Experimental Medicine (2001)

Epstein-Barr virus (EBV) latent membrane protein (LMP)2 is a multiple membrane spanning molecule which lacks ectodomains projecting into the lumen of the endoplasmic reticulum (ER). Human CD8+ cytotoxic T lymphocytes (CTL)s recognize a number of epitopes within LMP2. Assays with epitope-specific CTLs in two different cell backgrounds lacking the transporter associated with antigen processing (TAP) consistently show that some, but not all, LMP2 epitopes are presented in a TAP-independent manner. However, unlike published examples of TAP-independent processing from endogenously expressed antigens, presentation of TAP-independent LMP2 epitopes was abrogated by inhibition of proteasomal activity. We found a clear correlation between hydrophobicity of the LMP2 epitope sequence and TAP independence, and experiments with vaccinia minigene constructs expressing cytosolic epitope peptides confirmed that these more hydrophobic peptides were selectively able to access the HLA class I pathway in TAP-negative cells. Furthermore, the TAP-independent phenotype of particular epitope sequences did not require membrane location of the source antigen since (i) TAP-independent LMP2 epitopes inserted into an EBV nuclear antigen and (ii) hydrophobic epitope sequences native to EBV nuclear antigens were both presented in TAP-negative cells. We infer that there is a proteasome-dependent, TAP-independent pathway of antigen presentation which hydrophobic epitopes can selectively access.
Trimetrexate as biochemical modulator of 5-fluorouracil/leucovorin in advanced colorectal cancer: final results of a randomised European study
Authors: C.J.A. Punt, H.J. Keizer, J. Douma, T. Skovsgaard, J. Schüller, E.W. Muller, C.H.H. Ten Napel, J.J. Croles, H. Lochs, J. Zhang, L. Hammershaimb
Journal: Annals of Oncology (2002)
Effective pulmonary blood flow in normal children at rest.
Authors: J J Bowyer, J O Warner, D M Denison
Journal: Thorax (1988)

Effective pulmonary blood flow was measured with a soluble inert gas uptake method (10% argon, 3.5% freon-22, 35% oxygen, balance nitrogen) in 98 apparently healthy children aged 5-14 years. None had any evidence of cardiorespiratory disease and all had normal values for absolute and dynamic lung volumes and transfer factor for carbon monoxide. Values of blood flow measured by a rebreathing method correlated reasonably closely with height, weight, body surface area, and lung volumes, and to a lesser extent with hand and foot size. The mean (SD) effective pulmonary blood flow index was 2.7 (0.31) 1 min-1 m-2. Small children found a single breath method of measuring flow more difficult to perform and the results were more variable.
Topics, Thoughts, and Tendencies
Authors: P. T. O'Farrell
Journal: BMJ (1952)

When you did me the signal honour of appointing me President-Elect of the British Medical Association I took courage from some lines of the oft-quoted sentence, " Be not afraid of greatness . . .some have greatness thrust upon them."It is in this spirit that I now address you as President, first thanking you, my friends, for the distinction you
Interstitial lung diseases: an epidemiological overview
Authors: M. Demedts, A.U. Wells, J.M. Antó, U. Costabel, R. Hubbard, P. Cullinan, H. Slabbynck, G. Rizzato, V. Poletti, E.K. Verbeken, M.J. Thomeer, J. Kokkarinen, J.C. Dalphin, A. Newman Taylor
Journal: European Respiratory Journal (2001)

Epidemiological studies on interstitial lung diseases (ILDs) may be schematically subdivided into the following major types: 1) quantifications of disease, broken down into incidence, prevalence and mortality data; 2) identification of aetiological factors; and 3) clinical epidemiological studies. Epidemiological data may be obtained from different sources or population groups, using different study designs such as systematic national statistics, population-based data and registries, and large case series of specific diseases. Differences in results between epidemiological studies may be due to real differences in incidence, but may also be due to changes in disease definitions and classifications, differences in the epidemiological design of the studies, or even registration bias. Comparative epidemiological data of different ILDs are almost limited to the general population study in Bernalillo County and to national mortality statistics, which should be interpreted with great caution. Also, some, mostly national registries of the different ILDs have been carried out by specific medical profession groups (especially pulmonologists), which clearly underestimate the real incidence of ILDs, but in which the comparison of the relative frequencies is probably accurate. Based on all these comparative studies, sarcoidosis and idiopathic pulmonary fibrosis appear to be the most frequent ILDs, followed by hypersensitivity pneumonitis and ILD in collagen vascular disease, when classical pneumoconioses are not included. There is also a relatively large group of nonspecific fibrosis. Much more data have been published on the epidemiology of specific forms of interstitial lung disease. Most information is available on the epidemiology of sarcoidosis, and those data are probably the most accurate. Data on idiopathic pulmonary fibrosis have the disadvantage of the recent changes in definition and classification of this disease. Hypersensitivity pneumonitis has been studied epidemiologically, especially in some exposure groups such as farmers and pigeon breeders, and in some regions in North America, UK, France and Scandinavia. Estimates of frequencies of interstitial lung disease in collagen vascular disease or of drug-induced interstitial lung disease are less accurate and more variable, depending on diagnostic criteria. Notwithstanding the aforementioned problems, this report tries to provide a balanced overview of the epidemiology of different interstitial lung diseases.
DISPOSITION OF FIRST ADMISSIONS TO A PRIVATE PSYCHIATRIC HOSPITAL, 1920-1951
Authors: HAROLD H. MORRIS, MANLY Y. BRUNT
Journal: American Journal of Psychiatry (1957)

Four Groups of patients, each consisting of 1,000 consecutive first admissions to the Pennsylvania Hospital, have been followed for 5 years from the time of their first admission to a psychiatric hospital. The sample covers a span of more than 30 years in general psychiatric hospital experience in a large metropolitan area on the east coast. Tables show a decrease in death rates and in number of patients continuously hospitalized, with a relatively constant suicide rate. There has been a somewhat uniform readmission rate, but a tendency toward shorter duration of first admissions. The readmission and chronicity rates for the functional psychoses have been decreasing. Among the more important factors influencing the mortality rates are the introduction of more specific therapies for paresis in the late 1920's, chemotherapy in the late 1930's, antibiotics in the mid-1940's, and constantly improving standards of nursing and ancillary care throughout the whole period. Duration of stay has been influenced by changing policies regarding discharge, the use of somatic therapies, and increasing emphasis on the hospital as a therapeutic milieu. These factors favoring earlier discharge have not resulted in an increased readmission rate; on the contrary, the readmission rate for the functional psychoses has been lowered. When the total sample of patients is considered, fewer are dying in the 5 year period, more are leaving the hospital sooner, and about the same percentage is returning as in the early 1920's.
Induction of vascular smooth muscle cell expression of plasminogen activator inhibitor-1 by thrombin.
Authors: H Noda-Heiny, S Fujii, B E Sobel
Journal: Circulation Research (1993)

Local accumulation of plasminogen activator inhibitor-1 (PAI-1) in response to thrombosis has been implicated not only in inhibition of fibrinolysis but also in the pathogenesis of vascular disease. To determine whether thrombin, known to be released from thrombi, can induce expression of PAI-1 in vascular smooth muscle, bovine aortic smooth muscle cells were exposed to highly purified bovine thrombin. Thrombin, in the absence of serum, induced production of PAI-1 by bovine aortic smooth muscle cells in a dose-dependent manner. PAI-1 activity in the conditioned media reached a maximum with 12 nM thrombin. Metabolic labeling with [35S]methionine demonstrated that the elaborated PAI-1 was newly synthesized and that it comprised both a cleaved inactive 42-kd form and an uncleaved active 46-kd form. The increase of PAI-1 activity in the media paralleled the thrombin-induced increase in the concentration of the 46-kd form. Preincubation of thrombin with hirudin, a specific inhibitor of thrombin, or with D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone, an inhibitor of the active site of thrombin, prevented the induction of PAI-1 synthesis. The stimulatory effect of thrombin on PAI-1 synthesis was also evident at the level of expression of mRNA, with steady-state PAI-1 mRNA levels increasing by 100% in 4-8 hours. When the bovine aortic smooth muscle cells were exposed to transforming growth factor-beta 1, an agonist shown previously to increase PAI-1 synthesis in diverse cell types, synergy with thrombin was evident.(ABSTRACT TRUNCATED AT 250 WORDS)
Endothelial Vasodilation Effects of Statins in Type 2 Diabetic Patients
Authors: James R. Sowers
Journal: Diabetes Care (2002)

In this issue of Diabetes Care , there is an intriguing report of a double-blind, placebo-controlled, randomized study demonstrating that lipid-lowering treatment for 3 weeks with the powerful hydroxymethylglutaryl (HMG)-CoA reductase inhibitor (statin) atorvastatin did not reverse endothelium-dependent and -independent vascular dysfunction in 133 patients with type 2 diabetes (mean disease duration 11.5 years) and dyslipidemia (1). This observation is in stark contrast to results in nondiabetic dyslipidemic patients and insulin-resistant nondiabetic subjects in which HMG-CoA reductase therapy improved endothelium-dependent vascular relaxation (2–5). However, the study by van Venrooij et al. (1) is in agreement with a prior smaller study that observed no improvement in endothelial-derived vasodilation after statin treatment of established type 2 diabetic …
Metabolic reprogramming by viruses in the sunlit and dark ocean
Authors: Bonnie L Hurwitz, Steven J Hallam, Matthew B Sullivan
Journal: Genome biology (2013)

Abstract Background Marine ecosystem function is largely determined by matter and energy transformations mediated by microbial community interaction networks. Viral infection modulates network properties through mortality, gene transfer and metabolic reprogramming. Results Here we explore the nature and extent of viral metabolic reprogramming throughout the Pacific Ocean depth continuum. We describe 35 marine viral gene families with potential to reprogram metabolic flux through central metabolic pathways recovered from Pacific Ocean waters. Four of these families have been previously reported but 31 are novel. These known and new carbon pathway auxiliary metabolic genes were recovered from a total of 22 viral metagenomes in which viral auxiliary metabolic genes were differentiated from low-level cellular DNA inputs based on small subunit ribosomal RNA gene content, taxonomy, fragment recruitment and genomic context information. Auxiliary metabolic gene distribution patterns reveal that marine viruses target overlapping, but relatively distinct pathways in sunlit and dark ocean waters to redirect host carbon flux towards energy production and viral genome replication under low nutrient, niche-differentiated conditions throughout the depth continuum. Conclusions Given half of ocean microbes are infected by viruses at any given time, these findings of broad viral metabolic reprogramming suggest the need for renewed consideration of viruses in global ocean carbon models.
Influence of Dietary Zinc on Hepatic Collagen and Prolyl Hydroxylase Activity in Alcoholic Rats
Authors: América Giménez, Joan Caballería, Albert Parés, Silvia Alié, Ramón Deulofeu, Hernán Andreu, Joan Rodés
Journal: Hepatology (1992)

The effects of dietary zinc on hepatic collagen and prolyl hydroxylase activity in normal and alcoholic rats has been investigated in four groups of pair-fed male Wistar rats given either liquid ethanol or a control diet for 12 wk. Each group of pair-fed animals received a diet with a different zinc concentration (standard diet, 7.6 mg/L; low-zinc diet, 3.4 mg/L; zinc-supplemented diet, 76 mg/L; and zinc-extrasupplemented, 300 mg/L. There were no significant differences in hepatic collagen concentration and prolyl hydroxylase activity between alcoholic and normal rats receiving a standard diet (collagen, 77 +/- 5 and 73 +/- 6 micrograms/mg protein; and prolyl hydroxylase; 37 +/- 26 and 36 +/- 22 cpm/mg protein). Alcoholic rats fed a low-zinc diet showed increased prolyl hydroxylase activity (75 +/- 10 cpm/mg protein, p less than 0.05), although no changes in hepatic collagen (77 +/- 10 micrograms/mg protein) were observed in comparison with rats fed a standard alcoholic diet. By contrast, hepatic collagen was significantly lower in alcoholic rats fed a zinc-supplemented diet (66 +/- 4 and 63 +/- 3 micrograms/mg protein, p less than 0.05 and p less than 0.01, respectively), and hepatic prolyl hydroxylase activity was particularly lower in rats receiving zinc 300 mg/L (18 +/- 20 cpm/mg protein). Similar effects were observed in normal rats. We conclude that dietary zinc influences hepatic prolyl hydroxylase activity and collagen deposition in alcoholic rats, and in consequence, the control of dietary zinc is necessary to assess the effects of alcohol on collagen metabolism in rats.
Deep sequencing and de novo assembly of the mouse oocyte transcriptome define the contribution of transcription to the DNA methylation landscape
Authors: Lenka Veselovska, Sebastien A. Smallwood, Heba Saadeh, Kathleen R. Stewart, Felix Krueger, Stéphanie Maupetit-Méhouas, Philippe Arnaud, Shin-ichi Tomizawa, Simon Andrews, Gavin Kelsey
Journal: Genome biology (2015)

Previously, a role was demonstrated for transcription in the acquisition of DNA methylation at imprinted control regions in oocytes. Definition of the oocyte DNA methylome by whole genome approaches revealed that the majority of methylated CpG islands are intragenic and gene bodies are hypermethylated. Yet, the mechanisms by which transcription regulates DNA methylation in oocytes remain unclear. Here, we systematically test the link between transcription and the methylome. We perform deep RNA-Seq and de novo transcriptome assembly at different stages of mouse oogenesis. This reveals thousands of novel non-annotated genes, as well as alternative promoters, for approximately 10 % of reference genes expressed in oocytes. In addition, a large fraction of novel promoters coincide with MaLR and ERVK transposable elements. Integration with our transcriptome assembly reveals that transcription correlates accurately with DNA methylation and accounts for approximately 85–90 % of the methylome. We generate a mouse model in which transcription across the Zac1/Plagl1 locus is abrogated in oocytes, resulting in failure of DNA methylation establishment at all CpGs of this locus. ChIP analysis in oocytes reveals H3K4me2 enrichment at the Zac1 imprinted control region when transcription is ablated, establishing a connection between transcription and chromatin remodeling at CpG islands by histone demethylases. By precisely defining the mouse oocyte transcriptome, this work not only highlights transcription as a cornerstone of DNA methylation establishment in female germ cells, but also provides an important resource for developmental biology research.
The transforming growth factor- /Smad2,3 signalling axis is impaired in experimental pulmonary hypertension
Authors: A. Zakrzewicz, F. M. Kouri, B. Nejman, G. Kwapiszewska, M. Hecker, R. Sandu, E. Dony, W. Seeger, R. T. Schermuly, O. Eickelberg, R. E. Morty
Journal: European Respiratory Journal (2007)

Mutations in genes encoding members of the transforming growth factor (TGF)-β superfamily have been identified in idiopathic forms of pulmonary arterial hypertension (PAH). The current study examined whether perturbations to the TGF-β/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH. Expression of the TGF-β signalling machinery was assessed in the lungs and kidneys of MCT-treated rodents with severe PAH by semi-quantitative reverse-transcription (RT)-PCR, real-time RT-PCR and immunoblotting. TGF-β signalling was assessed in the lungs and in pulmonary artery smooth muscle cells (PASMC) from MCT-treated rodents by Smad2 phosphorylation, expression of the connective tissue growth factor gene, activation of the serpine promoter in a luciferase reporter system and by the induction of apoptosis. The expression of type1 TGF-β receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-β signalling and TGF-β-induced apoptosis, were dramatically reduced in the lungs and PASMC, but not the kidneys, of MCT-treated rodents that developed severe PAH. The current data indicate that the transforming growth factor-β/Smad2,3 signalling axis is functionally impaired in monocrotaline-treated rodents with severe pulmonary arterial hypertension, underscoring the potential importance of transforming growth factor-β/Smad2,3 signalling in the onset or development of pulmonary arterial hypertension.
Positive Bronchial Responses To D. Pteronyssinus In Subjects With Confirmed Local Allergic Rhinitis
Authors: P. Campo, C. Mayorga, C. Rondon, L. Galindo, R. Garcia, J. Garcia-Campos, L. Melendez, J. Rodriguez-Bada, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2012)
Completeness of main outcomes across randomized trials in entire discipline: survey of chronic lung disease outcomes in preterm infants
Authors: J. P. A. Ioannidis, J. D. Horbar, C. M. Ovelman, Y. Brosseau, K. Thorlund, M. E. Buus-Frank, E. J. Mills, R. F. Soll
Journal: BMJ (2015)

<b>Objective</b> To map the availability of information on a major clinical outcome—chronic lung disease—across the randomized controlled trials in systematic reviews of an entire specialty, specifically interventions in preterm infants. <b>Design</b> Survey of systematic reviews. <b>Data sources</b> Cochrane Database of Systematic Reviews. <b>Study selection and methods</b> All Cochrane systematic reviews (as of November 2013) that had evaluated interventions in preterm infants. We identified how many of those systematic reviews had looked for information on chronic lung disease, how many reported on chronic lung disease, and how many of the randomized controlled trials included in the systematic reviews reported on chronic lung disease. We also randomly selected 10 systematic reviews that did not report on chronic lung disease and 10 that reported on any such outcomes and identified whether any information on chronic lung disease appeared in the primary reports of the randomized controlled trials but not in the systematic reviews. <b>Main outcome measures</b> Whether availability of chronic lung disease outcomes differed by type of population and intervention and whether additional non-extracted data might have been available in trial reports. <b>Results</b> 174 systematic reviews with 1041 trials exclusively concerned preterm infants. Of those, 105 reviews looked for chronic lung disease outcomes, and 79 reported on these outcomes. Of the 1041 included trials, 202 reported on chronic lung disease at 28 days and 200 at 36 weeks postmenstrual; 320 reported on chronic lung disease with any definition. The proportion of systematic reviews that looked for or reported on chronic lung disease and the proportion of trials that reported on chronic lung disease was larger in preterm infants with respiratory distress or support than others (P&lt;0.001) and differed across interventions (P&lt;0.001). Even for trials on children with ventilation interventions, only 56% (48/86) reported on chronic lung disease. In the random sample, 45 of 84 trials (54%) had no outcomes on chronic lung disease in the systematic reviews, and only 9/45 (20%) had such information in the primary trial reports. <b>Conclusions</b> Most trials included in systematic reviews of interventions on preterm infants are missing information on one of the most common serious outcomes in this population. Use of standardized clinical outcomes that would have to be collected and reported by default in all trials in a given specialty should be considered.