tbuckley/cabot-search huggingface dataset:
A Genome Phylogeny for Mitochondria Among -Proteobacteria and a Predominantly Eubacterial Ancestry of Yeast Nuclear Genes
Authors: Christian Esser, Nahal Ahmadinejad, Christian Wiegand, Carmen Rotte, Federico Sebastiani, Gabriel Gelius-Dietrich, Katrin Henze, Ernst Kretschmann, Erik Richly, Dario Leister, David Bryant, Michael A Steel, Peter J Lockhart, David Penny, William Martin
Journal: Molecular Biology and Evolution (2004)

Analyses of 55 individual and 31 concatenated protein data sets encoded in Reclinomonas americana and Marchantia polymorpha mitochondrial genomes revealed that current methods for constructing phylogenetic trees are insufficiently sensitive (or artifact-insensitive) to ascertain the sister of mitochondria among the current sample of eight alpha-proteobacterial genomes using mitochondrially-encoded proteins. However, Rhodospirillum rubrum came as close to mitochondria as any alpha-proteobacterium investigated. This prompted a search for methods to directly compare eukaryotic genomes to their prokaryotic counterparts to investigate the origin of the mitochondrion and its host from the standpoint of nuclear genes. We examined pairwise amino acid sequence identity in comparisons of 6,214 nuclear protein-coding genes from Saccharomyces cerevisiae to 177,117 proteins encoded in sequenced genomes from 45 eubacteria and 15 archaebacteria. The results reveal that approximately 75% of yeast genes having homologues among the present prokaryotic sample share greater amino acid sequence identity to eubacterial than to archaebacterial homologues. At high stringency comparisons, only the eubacterial component of the yeast genome is detectable. Our findings indicate that at the levels of overall amino acid sequence identity and gene content, yeast shares a sister-group relationship with eubacteria, not with archaebacteria, in contrast to the current phylogenetic paradigm based on ribosomal RNA. Among eubacteria and archaebacteria, proteobacterial and methanogen genomes, respectively, shared more similarity with the yeast genome than other prokaryotic genomes surveyed.
A novel natural compound, a cycloanthranilylproline derivative (Fuligocandin B), sensitizes leukemia cells to apoptosis induced by tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) through 15-deoxy-Δ12, 14 prostaglandin J2 production
Authors: Hiroo Hasegawa, Yasuaki Yamada, Kanki Komiyama, Masahiko Hayashi, Masami Ishibashi, Toshiaki Sunazuka, Takeshi Izuhara, Kazuyuki Sugahara, Kazuto Tsuruda, Masato Masuda, Nobuyuki Takasu, Kunihiro Tsukasaki, Masao Tomonaga, Shimeru Kamihira
Journal: Blood (2007)
Patient survival on PAN/AN69 membrane hemodialysis
Authors: P K Chandran, R Liggett, B Kirkpatrick
Journal: Journal of the American Society of Nephrology (1993)

Survival characteristics over a 10-yr period of 352 patients on hemodialysis (HD) with polyacrylonitrile membranes in a single center were retrospectively analyzed and compared with national data collected by the U.S. Renal Data System (USRDS). Only those patients who stayed on HD for longer than 3 months were included. Any outcome other than death was considered as lost to follow-up. The number of expected deaths in the entire patient population according to the USRDS data base was 203, whereas the observed actual rate was only 132, reaching high statistical significance. Several subgroups of patients, stratified on the basis of age and time on starting HD, diabetes mellitus as the cause of original renal disease, etc., also exhibited significantly better survival. HD with a biocompatible membrane, providing adequate removal of low- as well as "middle"-molecular-weight uremic toxins, may be one important explanation for improved survival.
Effect of free radical altered IgG on allergic inflammation.
Authors: S D Hewitt, J Lunec, C J Morris, D R Blake
Journal: Annals of the Rheumatic Diseases (1987)

The rheumatoid synovium is capable of producing large amounts of IgG which may become modified by the actions of free radicals. A rat model of synovitis was established and challenged with both normal and free radical altered IgG. IgG was prepared from homologous pooled serum by high performance liquid chromatography, and free radical damage was induced by 15 minutes ultraviolet (UV) irradiation. The results showed a worsening in gross assessments of inflammation, increases in biochemical indices of lipid peroxidation, and also a rise in the proportion of IgG which, on reisolation, showed the characteristic fluorescence associated with free radical damage. This demonstrated how the presence of free radical altered IgG might convert an inflammatory insult to a more persistent stimulus, and the capacity of an environment subjected to continuing antigenic stimulation to induce further free radical damage to IgG.
Allogeneic cytotoxic T-cell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial
Authors: Tanzina Haque, Gwen M. Wilkie, Marie M. Jones, Craig D. Higgins, Gillian Urquhart, Phoebe Wingate, David Burns, Karen McAulay, Marc Turner, Christopher Bellamy, Peter L. Amlot, Deirdre Kelly, Alastair MacGilchrist, Maher K. Gandhi, Anthony J. Swerdlow, Dorothy H. Crawford
Journal: Blood (2007)
Biliary physiology in rats with bile ductular cell hyperplasia. Evidence for a secretory function of proliferated bile ductules.
Authors: G Alpini, R Lenzi, L Sarkozi, N Tavoloni
Journal: Journal of Clinical Investigation (1988)

To establish the role of the biliary epithelium in bile formation, we studied several aspects of biliary physiology in control rats and in rats with ductular cell hyperplasia induced by a 14-d extrahepatic biliary obstruction. Under steady-state conditions, spontaneous bile flow was far greater in obstructed rats (266.6 +/- 51.9 microliters/min per kg) than in controls (85.6 +/- 10.6 microliters/min per kg), while excretion of 3-hydroxy bile acids was the same in the two groups. Infusion of 10 clinical units (CU)/kg per h secretin produced a minimal choleretic effect in controls (+3.8 +/- 1.9 microliters/min per kg) but a massive increase in bile flow in the obstructed animals (+127.8 +/- 34.9 microliters/min per kg). Secretin choleresis was associated with an increase in bicarbonate biliary concentration and with a decline in [14C]mannitol bile-to-plasma ratio, although solute biliary clearance significantly increased. Conversely, administration of taurocholate (5 mumol/min per kg) produced the same biliary effects in control rats and in rats with proliferated biliary ductules. In the obstructed animals, the biliary tree volume measured during taurocholate choleresis (67.4 +/- 15.8 microliters/g liver) was significantly greater than that determined during the increase in bile flow induced by secretin (39.5 +/- 10.4 microliters/g liver). These studies indicate that, in the rat, the proliferated bile ductules/ducts spontaneously secrete bile and are the site of secretin choleresis. Furthermore, because the proliferated cells expressed phenotypic traits of bile ductular cells, our results suggest that whereas under normal conditions the biliary ductules/ducts in the rat seem to contribute little to bile formation, secretion of water and electrolytes is a property of biliary epithelial cells.
Transforming growth factor-beta. Murine glomerular receptors and responses of isolated glomerular cells.
Authors: K MacKay, L J Striker, J W Stauffer, T Doi, L Y Agodoa, G E Striker
Journal: Journal of Clinical Investigation (1989)

Proliferation of resident glomerular cells and the accumulation of mesangial matrix are histologic abnormalities which are observed in the course of many progressive glomerular diseases. We explored the potential regulatory effects of transforming growth factor-beta (TGF-beta) on these processes. We found that cultured mouse glomerular endothelial, mesangial, and epithelial cells as well as isolated intact rat glomeruli possess high-affinity receptors for TGF-beta. We also found that, although TGF-beta consistently inhibited the proliferation of glomerular endothelial and epithelial cells, it acted as a bifunctional regulator of mesangial cell proliferation. TGF-beta significantly increased the production of collagen and fibronectin by glomerular mesangial cells whereas only fibronectin production was augmented in glomerular epithelial cells. The presence of TGF-beta receptors on intact glomeruli and on each glomerular cell type and the demonstrated responsiveness of these cells to TGF-beta combine to suggest that potentially important interactions may occur between resident glomerular cells and TGF-beta in vivo.
Additive Antiproteinuric Effect of Pentoxifylline in Patients with Type 2 Diabetes under Angiotensin II Receptor Blockade
Authors: Juan F Navarro, Carmen Mora, Mercedes Muros, Javier García
Journal: Journal of the American Society of Nephrology (2005)

Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for &gt;1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (<i>n</i> = 30) or to a control group (<i>n</i> = 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-α (<i>R</i> = 0.53, <i>P</i> &lt; 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; <i>P</i> &lt; 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was −16.7 and 5.5%, respectively (between-group comparison, <i>P</i> &lt; 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-α also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (<i>P</i> &lt; 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-α in patients who were treated with PTF (<i>R</i> = 0.49, <i>P</i> &lt; 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-α excretion.
Extensive Chromosomal Instability in <i>Rad51d</i>-Deficient Mouse Cells
Authors: Phillip G. Smiraldo, Aaron M. Gruver, Joshua C. Osborn, Douglas L. Pittman
Journal: Cancer Research (2005)

Abstract Homologous recombination is a double-strand break repair pathway required for resistance to DNA damage and maintaining genomic integrity. In mitotically dividing vertebrate cells, the primary proteins involved in homologous recombination repair are RAD51 and the five RAD51 paralogs, RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3. In the absence of Rad51d, human and mouse cells fail to proliferate, and mice defective for Rad51d die before birth, likely as a result of genomic instability and p53 activation. Here, we report that a p53 deletion is sufficient to extend the life span of Rad51d-deficient embryos by up to 6 days and rescue the cell lethal phenotype. The Rad51d−/− Trp53−/− mouse embryo–derived fibroblasts were sensitive to DNA-damaging agents, particularly interstrand cross-links, and exhibited extensive chromosome instability including aneuploidy, chromosome fragments, deletions, and complex rearrangements. Additionally, loss of Rad51d resulted in increased centrosome fragmentation and reduced levels of radiation-induced RAD51-focus formation. Spontaneous frequencies of sister chromatid exchange were not affected by the absence of Rad51d, but sister chromatid exchange frequencies did fail to be induced upon challenge with the DNA cross-linking agent mitomycin C. These findings support a crucial role for mammalian RAD51D in normal development, recombination, and maintaining mammalian genome stability.
Gold treatment, nephrotic syndrome, and multi-organ failure in a patient with adult onset Still's disease
Authors: K S Eardley
Journal: Annals of the Rheumatic Diseases (2001)

A 25 year old Bengali woman presented acutely with a symmetrical inflammatory polyarthritis aVecting knees, wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints which had developed over six weeks. The distal interphalangeal joints were spared. She had a pigmented, scaly rash over the hands, chest, and back. There had been no fever, hair loss, mouth ulcers, genitourinary symptoms, Raynaud’s phenomenon, and no significant past medical history. At presentation there was no lymphadenopathy or organomegaly. Initial investigations showed (normal range): haemoglobin 106 g/l (135‐180 g/l), mean corpuscular volume 72.7 fl (76‐96 fl), white cell count (WCC) 18 × 10 9
1129 PRECLINICAL CHARACTERIZATION OF GS-9620, A POTENT AND SELECTIVE ORAL TLR7 AGONIST
Authors: P. Turnas, X. Zheng, B. Lu, G. Rhodes, P. Duatschek, J. Hesselgesser, C. Frey, I. Henne, A. Fosdick, R. Halcomb, G. Wolfgang
Journal: Journal of Hepatology (2011)
Treatment of advanced non-small-cell lung cancer patients with ECOG performance status 2: results of an European Experts Panel
Authors: C. Gridelli, A. Ardizzoni, T. Le Chevalier, C. Manegold, F. Perrone, N. Thatcher, N. van Zandwijk, M. Di Maio, O. Martelli, F. De Marinis
Journal: Annals of Oncology (2004)
Slow, stochastic transgene repression with properties of a timer.
Authors: Clifford L Wang, Desirée C Yang, Matthias Wabl
Journal: Genome biology (2006)

When gene expression varies unpredictably between genetically identical organisms, this is sometimes ascribed as stochastic. With the prevalence of retroviral vectors, stochastic repression is often observed and can complicate the interpretation of outcomes. But it may also faithfully reflect characteristics of sites in the genome.We created and identified several cell clones in which, within a given cell, retroviral transcription of a transgene was repressed heritably and essentially irreversibly. This repression was relatively slow; total repression in all cells took months. We observed the dynamics of repression and found that they were ergodic, that is, tending with a probability to a final state independent of previous conditions. Different positions of the transgene in the genome demonstrated different dynamics. At a position on mouse chromosome 9, repression abided by near perfect first-order kinetics and was highly reproducible, even under conditions where the number of cell generations per day varied.We propose that such a cell division independent 'off' mechanism could play a role in endogenous gene expression, potentially providing an epigenetically based timer for extended periods.
Feedback control of regulatory T cell homeostasis by dendritic cells in vivo
Authors: Guillaume Darrasse-Jèze, Stephanie Deroubaix, Hugo Mouquet, Gabriel D. Victora, Thomas Eisenreich, Kai-hui Yao, Revati F. Masilamani, Michael L. Dustin, Alexander Rudensky, Kang Liu, Michel C. Nussenzweig
Journal: The Journal of Experimental Medicine (2009)

CD4+CD25+Foxp3+ natural regulatory T cells (T reg cells) maintain self-tolerance and suppress autoimmune diseases such as type 1 diabetes and inflammatory bowel disease (IBD). In addition to their effects on T cells, T reg cells are essential for maintaining normal numbers of dendritic cells (DCs): when T reg cells are depleted, there is a compensatory Flt3-dependent increase in DCs. However, little is known about how T reg cell homeostasis is maintained in vivo. We demonstrate the existence of a feedback regulatory loop between DCs and T reg cells. We find that loss of DCs leads to a loss of T reg cells, and that the remaining T reg cells exhibit decreased Foxp3 expression. The DC-dependent loss in T reg cells leads to an increase in the number of T cells producing inflammatory cytokines, such as interferon γ and interleukin 17. Conversely, increasing the number of DCs leads to increased T reg cell division and accumulation by a mechanism that requires major histocompatibility complex II expression on DCs. The increase in T reg cells induced by DC expansion is sufficient to prevent type 1 autoimmune diabetes and IBD, which suggests that interference with this feedback loop will create new opportunities for immune-based therapies.
Cytokine regulation of epithelial permeability and ion transport
Authors: D M McKAY, A W BAIRD
Journal: Gut (1999)

The intestinal epithelium serves as a dynamic barrier which, in the course of its normal function, maintains regulated uptake of nutrients and water at the same time as excluding potential pathogens. Enteropathies, including inflammatory bowel disease (IBD) result in, or perhaps even from, perturbed epithelial function. Despite the idiopathic nature of IBD, it is apparent that much of the pathophysiology, tissue damage and symptomatology of these disorders are due to inappropriate or exaggerated immune reactions.1 2 Cytokines are, inter alia, regulators of both innate and acquired immunity, so therefore it is not surprising that exaggerated effects of cytokines in acute or chronic inflammatory states may be due to unregulated production of pro-inflammatory cytokines or inadequate synthesis of anti-inflammatory cytokines. Indeed, increases in cytokine concentrations in models of enteric inflammation or IBD are well documented.3 Here, we provide an overview of cytokine regulation of epithelial ion transport and permeability, highlighting, where appropriate, the potential of the epithelium to modulate mucosal immune reactions and its own function.

Relatively few studies have demonstrated cytokine effects on epithelial function in vivo or by examining intestinal tissue responses ex vivo.4 5 Several features contribute to difficulties with interpretation of such studies. Firstly, cytokines act in a coordinated interplay of often redundant, pleiotropic and occasionally opposing actions.6 Secondly, given the complex intercellular signalling that occurs within the gut,7cytokine effects may involve other, non-cytokine mediators.8-10 Finally, virtually every putative mediator of inflammation has been implicated in diseases of the intestine, representing at one time the academic pharmacologist’s dream and the therapist’s nightmare.

The advent of epithelial cell lines, principally the tumour derived T84, Caco-2 and HT-29 cell lines, has offered opportunities to study influences of cytokines on epithelial function by taking a reductionist approach. These cell lines, when grown on …
Human Papillomavirus Infection and Cervical Cytology in Women Screened for Cervical Cancer in the United States, 2003–2005
Authors: S. Deblina Datta, Laura A. Koutsky, Sylvie Ratelle, Elizabeth R. Unger, Judith Shlay, Tracie McClain, Beth Weaver, Peter Kerndt, Jonathan Zenilman, Michael Hagensee, Cristen J. Suhr, Hillard Weinstock
Journal: Annals of Internal Medicine (2008)

Background: Millions of women in the United States receive cervical screening in sexually transmitted disease (STD), family planning, and primary care clinical settings. Objective: To inform current cervical screening programs. Design: Measurement of abnormal Papanicolaou (Pap) tests and high-risk human papillomavirus (HPV) infection among demographically diverse women who received routine cervical screening from January 2003 to December 2005 in the United States. Setting: 26 STD, family planning, and primary care clinics in 6 U.S. cities. Patients: 9657 women age 14 to 65 years receiving routine cervical screening. Measurements: Pap test results and high-risk HPV prevalence by Hybrid Capture 2 assay (Digene, Gaithersburg, Maryland). Results: Among 9657 patients, overall high-risk HPV prevalence by Hybrid Capture 2 testing was 23% (95% CI, 22% to 24%). Prevalence was highest among women age 14 to 19 years (35% [CI, 32% to 38%]) and lowest among women age 50 to 65 years (6% [CI, 4% to 8%]). Prevalence by clinic type (adjusted for age and city) ranged from 26% (CI, 24% to 29%) in STD clinics to 17% (CI, 16% to 20%) in primary care clinics. Women younger than 30 years of age whose Pap test showed atypical squamous cells of undetermined significance had a high-risk HPV prevalence of 53%; women 30 years of age or older with normal Pap tests had a 9% prevalence. Values did not vary substantially by clinic type. Limitation: Hybrid Capture 2 and Pap testing were noncentralized, and consent was required for enrollment. Conclusion: High-risk HPV was widespread among women receiving cervical screening in the United States. Many women 30 years of age or older with normal Pap tests would need follow-up if Hybrid Capture 2 testing is added to cytology screening.
A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivo
Authors: Yoriko Saito, Hitomi Yuki, Mitsuo Kuratani, Yoshinobu Hashizume, Shinsuke Takagi, Teruki Honma, Akiko Tanaka, Mikako Shirouzu, Junko Mikuni, Noriko Handa, Ikuko Ogahara, Akiko Sone, Yuho Najima, Yuri Tomabechi, Motoaki Wakiyama, Naoyuki Uchida, Mariko Tomizawa-Murasawa, Akiko Kaneko, Satoshi Tanaka, Nahoko Suzuki, Hiroshi Kajita, Yuki Aoki, Osamu Ohara, Leonard D. Shultz, Takehiro Fukami, Toshio Goto, Shuichi Taniguchi, Shigeyuki Yokoyama, Fumihiko Ishikawa
Journal: Science Translational Medicine (2013)

A pyrrolo-pyrimidine kinase inhibitor, RK-20449, eliminates chemotherapy-resistant human primary AML stem cells in vivo.
Intravenous rehydration in paediatric gastroenteritis
Authors: A. L. Nager
Journal: BMJ (2011)

The rehydration of dehydrated children can be seriously challenging. Many factors need to be taken into account when choosing the most appropriate route and method of rehydration, including the setting, equipment, personnel, skill level, volume of patients, and available resources. Fortunately, in the emergency department, all types of rehydration—including oral, nasogastric, and intravenous—should be feasible.