tbuckley/cabot-search huggingface dataset:
The angiotensin II receptor antagonist losartan reduces blood pressure but not renal injury in obese Zucker rats.
Authors: G S Crary, S K Swan, M P O'Donnell, B L Kasiske, S A Katz, W F Keane
Journal: Journal of the American Society of Nephrology (1995)

Agents that interfere with the renin-angiotensin system (RAS) may ameliorate progressive renal injury, particularly in a setting where intrarenal RAS activity appears to be elevated. Whether RAS antagonists affect renal disease progression when intrarenal RAS activity is not increased is unclear. In this study, therefore, the effects of the angiotensin II receptor antagonist losartan on glomerular and tubulointerstitial injury were investigated in obese Zucker rats (OZR), an experimental model of progressive renal disease characterized by reduced intrarenal renin content and reduced plasma renin activity. Losartan (100 or 200 mg/L of drinking water) was administered to OZR beginning at 26 wk of age, when renal disease was established. At 38 and 44 wk of age, losartan-treated OZR demonstrated significant (P < 0.05) dose-related decreases in systolic blood pressure, compared with blood pressures in untreated, control OZR. Despite the reductions in blood pressure, losartan had no significant effects on albuminuria or glomerular or tubulointerstitial injury. At 44 wk of age, the percentage (mean +/- SE) of glomeruli with sclerosis was 51 +/- 11, 49 +/- 9, and 39 +/- 14% in control OZR, low-dose (100 mg/L) losartan-treated OZR, and high-dose (200 mg/L) losartan-treated OZR, respectively (P > 0.05). Similarly, the tubulointerstitial injury score (range, 0 to 4) in the three groups was, respectively, 1.7 +/- 0.4, 1.6 +/- 0.3, and 1.5 +/- 0.3 (P > 0.05). It was concluded that in a setting of chronic renal failure where intrarenal RAS activity does not appear to be increased, angiotensin II receptor antagonism may not be nephroprotective despite a reduction in blood pressure.
Insect Symbiosis: Derivation of Yeast-like Endosymbionts Within an Entomopathogenic Filamentous Lineage
Authors: Sung-Oui Suh, Hiroaki Noda, Meredith Blackwell
Journal: Molecular Biology and Evolution (2001)

Yeast-like endosymbionts (YLSs) of insects often are restricted to specific hosts and are essential to the host's survival. For example, in planthoppers (Homoptera: Delphacidae), endosymbionts function in sterol utilization and nitrogen recycling for the hosts. Our study, designed to investigate evolutionary changes in the YLS lineage involved in the planthopper association, strongly suggests an origin of the YLSs from within the filamentous ascomycetes (Euascomycetes), not the true yeasts (Saccharomycetes), as their morphology might indicate. During divergence of the planthopper YLSs, dramatic changes would have occurred in the insect-fungus interaction and the fungal morphology that have previously been undescribed in filamentous ascomycetes. Phylogenetic trees were based on individual and combined data sets of 2.6 kb of the nuclear small- and large-subunit ribosomal RNA genes for YLSs from three rice planthoppers (Laodelphax striatellus, Nilaparvata lugens, and Sogatella furcifera) compared with 56 other fungi. Parsimony analysis placed the planthopper YLSs within Cordyceps (Euascomycetes: Hypocreales: Clavicipitaceae), a genus of filamentous insects and a few fungal pathogenic ascomycetes. Another YLS species restricted to the aphid Hamiltonaphis styraci (Homoptera: Aphididae) was a sister taxon to the planthopper YLSS: Filamentous insect pathogens (Metarhizium and Beauveria) specific to the same species of insect hosts as the YLSs also formed lineages within the Clavicipitaceae, but these were distinct from the clade comprising YLS species. Trees constrained to include the YLSs in families of the Hypocreales other than the Clavicipitaceae were rejected by the Kishino-Hasegawa test. In addition, the results of this study support a hypothesis of two independent origins of insect-associated YLSs from among filamentous ascomycetes: the planthopper YLSs in the Clavicipitaceae and the YLSs associated with anobiid beetles (Symbiotaphrina species). Several lineages of true yeasts (Saccharomycetes) also formed endosymbiotic associations with beetles, but they were not closely related to either group derived from the filamentous ascomycetes.
Molecular Pathways: Targeting Mechanisms of Asbestos and Erionite Carcinogenesis in Mesothelioma
Authors: Michele Carbone, Haining Yang
Journal: Clinical Cancer Research (2011)

Abstract Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-κB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16INK4a and p14ARF are frequently inactivated in human mesothelioma, and ∼50% of mesotheliomas contain the NF2 mutation. Molecular therapies aimed at interfering with these pathways have not improved the dismal prognosis of mesothelioma, except possibly for a small subset of patients who benefit from certain therapies. Recent studies have shown the importance of asbestos-induced inflammation in the initiation and growth of mesothelioma, and HMGB1 and Nalp3 inflammasome have been identified as key initiators of this process. Asbestos induces cell necrosis, causing the release of HMGB1, which in turn may activate Nalp3 inflammasome, a process that is enhanced by asbestos-induced production of reactive oxygen species. HMGB1 and Nalp3 induce proinflammatory responses and lead to interleukin-1β and TNF-α secretion and NF-κB activity, thereby promoting cell survival and tumor growth. Novel strategies that interfere with asbestos- and erionite-mediated inflammation might prevent or delay the onset of mesothelioma in high-risk cohorts, including genetically predisposed individuals, and/or inhibit tumor growth. The very recent discovery that germline BAP1 mutations cause a new cancer syndrome characterized by mesothelioma, uveal melanoma, and melanocytic tumors provides researchers with a novel target for prevention and early detection. Clin Cancer Res; 18(3); 598–604. ©2011 AACR.
Chronic Pressor Effect of Kidney Extracts Containing Renin in Experimental Hypertensions
Authors: G. E. WAKERLIN, S. KREMEN, M. H. FRANK, H. E. SCHMID, L. GRAHAM, B KEITH
Journal: Circulation Research (1954)

A course of daily intramuscular injections of dog renin produced a maintained chronic pressor effect persisting for months during and following the renin injections in a majority of renal hypertensive dogs. Semipurified hog renin produced a temporary chronic pressor effect persisting for several weeks or somewhat longer but not throughout the renin injections in a minority of renal hypertensive dogs. The maintained chronic pressor effect was obtained only in the absence of antirenin; the temporary chronic pressor effect was lost when antirenin appeared in the plasma. Normotensive dogs were significantly less responsive to the chronic pressor effect of dog and hog renins than were renal hypertensive dogs. The mechanism of the chronic pressor effects is unknown.
Ingredients for successful online dating are outlined in evidence based study
Authors: Z. Kmietowicz
Journal: BMJ (2015)

In the world of online dating, choosing a screen name starting with a letter from the first half of the alphabet is as important as an attractive photo and a fluent headline, researchers have found. They scoured studies on the art of attraction and persuasion to find which factors are most likely to result in a face to face meeting.

Of almost 4000 studies in the fields of psychology, sociology, computer, behavioural, and neurocognitive sciences, 86 met the researchers’ inclusion criteria. The study findings were …
Degradation kinetic study of lysine in lysine hydrochloride solutions for injection by determining its main degradation product
Authors: Mengying Tao, Meng Zhu, Chunnuan Wu, Zhonggui He
Journal: Asian Journal of Pharmaceutical Sciences (2014)

A limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far. In the present work, the thermal degradation kinetics of lysine hydrochloride solutions for injection, the special solvent for ademetionine 1, 4-butanedisulfonate (SAM) for injection, was investigated at selected temperatures and pH values. The main degradation product of lysine was separated, purified, and confirmed as lysine lactam. A reversed-phase high performance liquid chromatographic (RP-HPLC) method without derivation was developed for the simultaneous determination of lysine and lysine lactam. The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics. The degradation and generation rate constants increased with increasing temperatures and decreasing pH values. The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol, respectively. Meanwhile, a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy. Considering there could be other side effects, we established an upper limit of lysine lactam (500 μg/ml), as the acceptable criteria for stability to estimate the shelf life together with lysine, which made the prediction more accurate and credible. Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature.
Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS)
Authors: Ariel C. Bulua, Anna Simon, Ravikanth Maddipati, Martin Pelletier, Heiyoung Park, Kye-Young Kim, Michael N. Sack, Daniel L. Kastner, Richard M. Siegel
Journal: The Journal of Experimental Medicine (2011)

Reactive oxygen species (ROS) have an established role in inflammation and host defense, as they kill intracellular bacteria and have been shown to activate the NLRP3 inflammasome. Here, we find that ROS generated by mitochondrial respiration are important for normal lipopolysaccharide (LPS)-driven production of several proinflammatory cytokines and for the enhanced responsiveness to LPS seen in cells from patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS), an autoinflammatory disorder caused by missense mutations in the type 1 TNF receptor (TNFR1). We find elevated baseline ROS in both mouse embryonic fibroblasts and human immune cells harboring TRAPS-associated TNFR1 mutations. A variety of antioxidants dampen LPS-induced MAPK phosphorylation and inflammatory cytokine production. However, gp91phox and p22phox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits are dispensable for inflammatory cytokine production, indicating that NADPH oxidases are not the source of proinflammatory ROS. TNFR1 mutant cells exhibit altered mitochondrial function with enhanced oxidative capacity and mitochondrial ROS generation, and pharmacological blockade of mitochondrial ROS efficiently reduces inflammatory cytokine production after LPS stimulation in cells from TRAPS patients and healthy controls. These findings suggest that mitochondrial ROS may be a novel therapeutic target for TRAPS and other inflammatory diseases.
Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity
Authors: Barbara Hrdlickova, Vinod Kumar, Kartiek Kanduri, Daria V Zhernakova, Subhash Tripathi, Juha Karjalainen, Riikka J Lund, Yang Li, Ubaid Ullah, Rutger Modderman, Wayel Abdulahad, Harri Lähdesmäki, Lude Franke, Riitta Lahesmaa, Cisca Wijmenga, Sebo Withoff
Journal: Genome Medicine (2014)

Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). lncRNAs are known to show more cell-type specificity than protein-coding genes. We aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AIDs which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes (granulocytes, monocytes, natural killer (NK) cells, B cells, memory T cells, naive CD4+ and naive CD8+ T cells) and four populations of cord blood-derived T-helper cells (precursor, primary, and polarized (Th1, Th2) T-helper cells). We show that lncRNAs mapping to loci shared between AID are significantly enriched in immune cell types compared to lncRNAs from the whole genome (α <0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five different cell types enriched (α <0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, and psoriasis; memory T and CD8+ T cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis). Furthermore, we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved. The observed enrichment of lncRNA transcripts in AID loci implies lncRNAs play an important role in AID etiology and suggests that lncRNA genes should be studied in more detail to interpret GWAS findings correctly. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways.
Intrinsic Factor-mediated Attachment of Vitamin B12 to Brush Borders and Microvillous Membranes of Hamster Intestine*
Authors: Robert M. Donaldson, Iain L. Mackenzie, Jerry S. Trier
Journal: Journal of Clinical Investigation (1967)

Hamster intrinsic factor (IF) preparations markedly enhanced the uptake of (57)cobalt-labeled cyanocobalamin (B(12)-(57)Co) by brush borders and microvillous membranes isolated from villous absorptive cells obtained from the distal but not the proximal half of hamster intestine. A similar effect was observed with rat and rabbit IF preparations, but IF preparations obtained from man, dog, and hog were ineffective. After fractionation of hamster IF preparations by gel filtration or ion exchange chromatography, the extent to which each fraction enhanced B(12)-(57)Co uptake by brush borders correlated closely with the vitamin B(12) binding capacity of the fraction. IF-mediated attachment of B(12)-(57)Co to brush borders occurred rapidly, was not diminished by removal of glucose or oxygen from the incubation medium, and was not significantly altered when incubation temperatures were reduced from 37 degrees C to 7 degrees C. Marked reduction in uptake occurred, however, in the absence of divalent cations. IF enhanced B(12)-(57)Co uptake by brush borders isolated from the proximal half of the intestine when these proximal brush borders were preincubated with supernatant fluid obtained after centrifugation of homogenates of distal intestinal mucosa at 28,500 g. The factor in this supernate responsible for the effect on proximal brush borders was shown to be particulate in nature upon centrifugation at speeds of 54,500 g or greater. The resultant pellet contained ribosomes and membranous fragments. Prolonged incubation of brush borders with crude saline extracts of hamster gastric mucosa resulted in decreased uptake of B(12)-(57)Co and marked lysis of brush borders with concomitant release of tissue nitrogen. Neither lysis of brush borders nor decreased uptake of B(12)-(57)Co with prolonged incubation was observed when hamster IF was partially purified. Furthermore, uptake of B(12)-(57)Co by brush borders increased with increasing purity of the IF preparation used. These results demonstrate IF-mediated attachment of B(12)-(57)Co to brush borders and microvillous membranes of hamster intestinal cells and provide further support for the presence of a specific receptor for IF-bound vitamin B(12) at the microvillous surface of the intestinal cell. IF-mediated attachment to the intestinal cell surface appears to be facilitated by divalent cations and to result from adsorption rather than an energy-requiring enzymatic reaction. Crude sources of hamster IF contain a factor which causes lysis of brush borders in vitro and which may explain in part the inhibitory effects of IF excess previously observed in vitro.
EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: F. Sargent Cheever, J. Howard Mueller
Journal: The Journal of Experimental Medicine (1947)

1. The disease was almost certainly infectious. 2. Its eradication offered much greater practical difficulties than are presented by certain other infections of mice. 3. A definite tendency toward greater susceptibility in first litters as contrasted with subsequent ones was noted. 4. Advantage could be taken of this increasing resistance to keep the infected colony in efficient production, but accidental loss of the stock prevented the continuation of the plan for a time sufficient to exclude possible failure due to seasonal variation. 5. Multiple etiologies may well have existed even within this circumscribed outbreak. 6. Experimental investigation of the condition offers extraordinary difficulties but its thorough understanding promises to bring new light to basic problems of disease.
Pulmonary granulomas after tumour necrosis factor alpha antagonist therapy
Authors: S R Vavricka
Journal: Thorax (2003)

Tumour necrosis factor α (TNFα) antagonists are an established therapeutic option in Crohn9s disease and rheumatoid arthritis. In recently published studies these agents have been used with great success, but little is known about any side effects or long term consequences. They increase the frequency of infections with mycobacteria, where TNFα is thought to be an important host defence factor. We describe one patient who was treated with TNFα antagonists and later developed pulmonary granulomas with caseating necrosis without detection of mycobacteria or any other pathogens. Possible mechanisms involved in this newly recognised side effect are discussed.
Functional murine interleukin 6 receptor with the intracisternal A particle gene product at its cytoplasmic domain. Its possible role in plasmacytomagenesis.
Authors: T Sugita, T Totsuka, M Saito, K Yamasaki, T Taga, T Hirano, T Kishimoto
Journal: The Journal of Experimental Medicine (1990)

Two species of the cDNAs encoding murine IL-6-R (one is abnormal and the other authentic) have been cloned from a plasmacytoma cell line, P3U1, and BALB/c mouse spleen cDNA libraries. In the cDNA encoding the abnormal IL-6-R, the region corresponding to an intracytoplasmic domain was replaced with a part of the long terminal repeat of the intracisternal A particle gene (IAP-LTR). The authentic IL-6-R consists of 460 amino acids with the domain of the Ig superfamily. The overall homology between murine and human IL-6-R was 69 and 54% at DNA and protein levels, respectively. The extracellular domain after the Ig-like domain of murine IL-6-R was found to have an homology with those of murine erythropoietin R, human IL-2-R beta chain, murine IL-4-R, and human granulocyte-macrophage CSF-R, as in the case of human IL-6-R, and these receptors have been classified as members of the IL receptor family. In P3U1 cells, the expression of the mRNA encoding abnormal IL-6-R was much higher than that of the mRNA encoding authentic IL-6-R. An IL-6-dependent human T cell line, KT-3, which did not respond to murine IL-6, acquired the responsiveness to murine IL-6 when transfected with the cDNA encoding abnormal IL-6-R, indicating that abnormal IL-6-R lacking a normal cytoplasmic domain can function. Since IL-6 functions as a potent growth factor for murine plasmacytomas, over-expression of abnormal IL-6-R may function as a positive selection element for the development of certain plasmacytomas.
The influence of personal tobacco smoking on the clinical practice of Italian chest physicians
Authors: S Nardini, R Bertoletti, V Rastelli, CF Donner
Journal: European Respiratory Journal (1998)

Tobacco smoking (TS) is a major cause of lung diseases. This study aimed to determine: 1) the prevalence of TS among chest physicians; 2) the influence of the personal smoking habit on clinical practice; and 3) what training about tobacco-related issues (TI) doctors received in medical school. A total of 983 attendees at the National Meeting of the Italian National Thoracic Society (AIPO) received a questionnaire about TI, which also contained the Fagerstroem Tolerance Questionnaire, and 605 (61.5%) answered. An independent assessment of the prevalence of smokers was carried out to minimize the bias of self-selection. The numbers of smokers was 151 (25%), never-smokers 246 (40.7%) and exsmokers 208 (34.4%). Smoking chest physicians underestimate the health hazards of smoking (p<0.001) and disregard their educational role (p=0.005) more than nonsmoking chest physicians. Compliance with smoking restrictions inside hospitals is frequently poor (30.1% smoke in clinics). In 33.1% of smokers a high nicotine addiction was found, which influenced their behaviour in hospital but not their ability to cope with tobacco-related problems. This ability was generally low: 39.1% of responders reported no training about TI. Smoking is frequent among Italian chest physicians, who are poorly trained about the health effects of tobacco smoking and are poorly skilled in treating smokers.